The use of the traditional American Joint Committee on Cancer(AJCC)staging system alone has limitations in predicting the survival of gingiva squamous cell carcinoma(GSCC)patients.We aimed to establish a comprehensive...The use of the traditional American Joint Committee on Cancer(AJCC)staging system alone has limitations in predicting the survival of gingiva squamous cell carcinoma(GSCC)patients.We aimed to establish a comprehensive prognostic nomogram with a prognostic value similar to the AJCC system.Methods:Patients were identified from SEER database.Variables were selected by a backward stepwise selection method in a Cox regression model.A nomogram was used to predict cancer-specific survival rates for 3,5 and 10 years in patients with GSCC.Several basic features of model validation were used to evaluate the performance of the survival model:consistency index(C-index),receiver operating characteristic(ROC)curve,calibration chart,net weight classification improvement(NRI),comprehensive discriminant improvement(IDI)and decision curve analysis(DCA).Results:Multivariate analyses revealed that age,race,marital status,insurance,AJCC stage,pathology grade and surgery were risk factors for survival.In particular,the C-index,the area under the ROC curve(AUC)and the calibration plots showed good performance of the nomogram.Compared to the AJCC system,NRI and IDI showed that the nomogram has improved performance.Finally,the nomogram's 3-year and 5-year and 10-year DCA curves yield net benefits higher than traditional AJCC,whether training set or a validation set.Conclusion:We developed and validated the first GSCC prognosis nomogram,which has a better prognostic value than the separate AJCC staging system.Overall,the nomogram of this study is a valuable tool for clinical practice to consult patients and understand their risk for the next 3,5 and 10 years.展开更多
Objectives:This study aimed to test the association between of type and number of D'Amico high-risk criteria(DHRCs)with cancer-specific mortality(CSM)in high-risk prostate cancer patients treated with radical pros...Objectives:This study aimed to test the association between of type and number of D'Amico high-risk criteria(DHRCs)with cancer-specific mortality(CSM)in high-risk prostate cancer patients treated with radical prostatectomy.Materials and methods:In the Surveillance,Epidemiology,and End Results database(2004–2016),we identified 31,281 radical prostatectomy patients with at least 1 DHRC,namely,prostate-specific antigen(PSA)>20 ng/mL(hrPSA),biopsy Gleason Grade Group(hrGGG)score of 4 and 5,or clinical tumor stage≥T3(hrcT).Multivariable Cox regression models and competing risks regression models(adjusting for other cause mortality)tested the association between DHRCs and 5-year CSM.Results:Of 31,281 patients,14,394(67%)exclusively harbored hrGGG,3189(15%)harbored hrPSA,and 1781(8.2%)harbored hrcT.Only 2132 patients(6.8%)harbored a combination of the 2 DHRCs,and 138(0.6%)had all 3 DHRCs.Five-year CSMrates ranged from 0.9%to 3.0%when any individual DHRC was present(hrcT,hrPSA,and hrGGG,in that order),1.6%to 5.9%when 2 DHRCs were present(hrPSA-hrcT,hrcT-hrGGG,and hrPSA-hrGGG,in that order),and 8.1%when all 3 DHRCs were present.Cox regression models and competing risks regression confirmed the independent predictor status of DHRCs for 5-year CSM that was observed in univariable analyses,with hazard ratios from 1.00 to 2.83 for 1 DHRC,2.35 to 5.88 for combinations of 2 DHRCs,and 7.13 for all 3 DHRCs.Conclusions:Within individual DHRCs,hrcT and hrPSA exhibited weaker effects than hrGGG did.Moreover,a dose-response effect was identified according to the number of DHRCs.Accordingly,the type and number of DHRCs allow further risk stratification within the high-risk subgroup.展开更多
Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC a...Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.展开更多
Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer cells.However,the conventional ATP biosensing strat-egy is o...Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer cells.However,the conventional ATP biosensing strat-egy is often limited by the undesired on-target off-tumor interference.Here,we reported a novel strategy to design enzymatically controlled DNA tetrahedron nanoprobes(En-DT)for biosensing and imaging ATP in tumor cells.The En-DT was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on the DNA tetrahedron.The En-DT could be catalytically activated by apurinic/apyrimidinic endonuclease 1(APE1)in cancer cells,but they did not respond to ATP in normal cells,thereby enabling cancer-specific ATP biosensing and imaging in vitro and in vivo with improved tumor specificity.This strategy would facilitate the precise detection of a broad range of biomarker in tumors and may promote the development of smart probes for cancer diagnosis.展开更多
Background and Objective The effectiveness of radiofrequency ablation(RFA)in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma(HCC)measuring 5 cm or less remains uncertain.Thi...Background and Objective The effectiveness of radiofrequency ablation(RFA)in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma(HCC)measuring 5 cm or less remains uncertain.This study was designed to elucidate the impact of RFA therapy on the survival outcomes of these patients and to construct a prognostic model for patients following RFA.Methods This study was performed using the Surveillance,Epidemiology,and End Results(SEER)database from 2004 to 2017,focusing on patients diagnosed with a solitary HCC lesion≤5 cm in size.We compared the overall survival(OS)and cancer-specific survival(CSS)rates of these patients with those of patients who received hepatectomy,radiotherapy,or chemotherapy or who were part of a blank control group.To enhance the reliability of our findings,we employed stabilized inverse probability treatment weighting(sIPTW)and stratified analyses.Additionally,we conducted a Cox regression analysis to identify prognostic factors.XGBoost models were developed to predict 1-,3-,and 5-year CSS.The XGBoost models were evaluated via receiver operating characteristic(ROC)curves,calibration plots,decision curve analysis(DCA)curves and so on.Results Regardless of whether the data were unadjusted or adjusted for the use of sIPTWs,the 5-year OS(46.7%)and CSS(58.9%)rates were greater in the RFA group than in the radiotherapy(27.1%/35.8%),chemotherapy(32.9%/43.7%),and blank control(18.6%/30.7%)groups,but these rates were lower than those in the hepatectomy group(69.4%/78.9%).Stratified analysis based on age and cirrhosis status revealed that RFA and hepatectomy yielded similar OS and CSS outcomes for patients with cirrhosis aged over 65 years.Age,race,marital status,grade,cirrhosis status,tumor size,and AFP level were selected to construct the XGBoost models based on the training cohort.The areas under the curve(AUCs)for 1,3,and 5 years in the validation cohort were 0.88,0.81,and 0.79,respectively.Calibration plots further demonstrated the consistency between the predicted and actual values in both the training and validation cohorts.Conclusion RFA can improve the survival of patients diagnosed with a solitary HCC lesion≤5 cm.In certain clinical scenarios,RFA achieves survival outcomes comparable to those of hepatectomy.The XGBoost models developed in this study performed admirably in predicting the CSS of patients with solitary HCC tumors smaller than 5 cm following RFA.展开更多
Objective: To explore the prognostic value of log odds of positive lymph nodes (LODDS) in patients with gastroenteropancreatic neuroendocrine tumors (GEPNET) and to develop nomograms based on LODDS for predicting 1-ye...Objective: To explore the prognostic value of log odds of positive lymph nodes (LODDS) in patients with gastroenteropancreatic neuroendocrine tumors (GEPNET) and to develop nomograms based on LODDS for predicting 1-year, 3-year, and 5-year overall survival (OS) and cancer-specific survival (CSS). Methods: This retrospective cohort study was based on the Surveillance, Epidemiology, and End Results (SEER) Program. Demographic data, clinical data, and survival status were extracted, with endpoints of OS and CSS. Multivariate Cox proportional hazards regression analysis assessed predictors associated with OS and CSS, with hazard ratios (HRs) and 95% confidence intervals (CIs) evaluated. Nomogram performance was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC). Results: A total of 1,673 patients were included and divided into a training set (n = 1,172) and a testing set (n = 501). Multivariate Cox proportional hazards regression analyses identified LODDS as an independent prognostic factor for OS (HR = 1.79, 95% CI: 1.44-2.24) and CSS (HR = 1.81, 95% CI: 1.41-2.31). The OS and CSS nomograms, developed from multivariate Cox regression analyses, showed good performance, with AUCs of 0.858, 0.878, and 0.852 for predicting 1-year, 3-year, and 5-year OS, and AUCs of 0.859, 0.887, and 0.865 for 1-year, 3-year, and 5-year CSS in the testing set. The nomograms are accessible online (OS: https://zhmte.shinyapps.io/DynNomapp/;CSS: https:// zhmty.shinyapps.io/DynNomapp/). Conclusions: LODDS serves as an independent prognostic factor in GEPNET. Online nomograms based on LODDS demonstrated effective performance in predicting OS and CSS in GEPNET patients, providing a convenient tool for clinical application.展开更多
Objective:To validate the 8 th edition of the American Joint Committee on Cancer(AJCC)staging system for pancreatic ductal adenocarcinoma(PDAC)in a Chinese cohort of radically resected patients and to develop a refine...Objective:To validate the 8 th edition of the American Joint Committee on Cancer(AJCC)staging system for pancreatic ductal adenocarcinoma(PDAC)in a Chinese cohort of radically resected patients and to develop a refined staging system for PDAC.Methods:Data were collected from the China Pancreas Data Center(CPDC)for patients with resected PDAC in 2016 and 2017,and cancer-specific survival(CSS)was evaluated using the Kaplan-Meier method and log-rank test.Univariate and multivariate analyses based on Cox regression were performed to identify prognostic factors.The recursive partitioning analysis(RPA),Kaplan-Meier method,and log-rank test were performed on the training dataset to generate a proposed modification for the 8 th TNM staging system utilizing the preoperative carbohydrate antigen(CA)19-9 level.Validation was performed for both staging systems in the validation cohort.Results:A total of 1,676 PDAC patients were retrieved,and the median CSS was significantly different between the 8 th TNM groupings,with no significant difference in survival between stage IB and IIA.The analysis of T and N stages demonstrated a better prognostic value in the N category.Multivariate analysis showed that the preoperative serum CA19-9 level was the strongest prognostic indicator among all the independent risk factors.All patients with CA19-9>500 U/mL had similar survival,and we proposed a new staging system by combining IB and IIA and stratifying all patients with high CA19-9 into stage III.The modified staging system had a better performance for predicting CSS than the 8 th AJCC staging scheme.Conclusions:The 8 th AJCC staging system for PDAC is suitable for a Chinese cohort of resected patients,and the N category has a better prognostic value than the T category.Our modified staging system has superior accuracy in predicting survival than the 8 th AJCC TNM staging system.展开更多
Background:Several studies suggested that hypertension is positively related to cancer incidence and mortality.In this study,we investigated the association between perioperative blood pressure(BP) and long?term survi...Background:Several studies suggested that hypertension is positively related to cancer incidence and mortality.In this study,we investigated the association between perioperative blood pressure(BP) and long?term survival out?comes in patients with rectal cancer.Methods:This study included a cohort of 358 patients with stages I–III rectal cancer who underwent a curative resection between June 2007 and June 2011.Both pre? and postoperative BPs were measured,by which patients were grouped(low BP:<120/80 mm Hg;high BP:ints were di≥120/80 mm Hg).The survival outcomes were compared between these two groups.The primary endposease?free survival(DFS) and cancer?specific survival(CSS).Results:Univariate analysis showed that patients with high preoperative systolic BP had lower 3?year DFS(67.2% vs.82.1%,P = 0.041) and CSS rates(81.9% vs.94.8%,P = 0.003) than patients with low preoperative systolic BP,and the associations remained significant in the Cox multivariate analysis,with the adjusted hazard ratios equal to 1.97 [95% confidence interval(CI) = 1.08–3.60,P = 0.028] and 2.85(95% CI = 1.00–8.25,P = 0.050),respectively.Similarly,in postoperative evaluation,patients with high systolic BP had significantly lower 3?year CSS rates than those with low systolic BP(78.3% vs.88.9%,P = 0.032) in univariate analysis.Moreover,high pre? and/or postoperative systolic BP presented as risk factors for CSS in the subgroups of patients who did not have a history of hypertension,with and/or without perioperative administration of antihypertensive drugs.Conclusions:High preoperative systolic BP was an independent risk factor for both CSS and DFS rates,and high postoperative systolic BP was significantly associated with a low CSS rate in rectal cancer patients.Additionally,our results suggest that rectal cancer patients may get survival benefit from BP control in perioperative care.However,further studies should be conducted to determine the association between BP and CSS and targets of BP control.展开更多
BACKGROUND There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas.AIM To develop comprehensive nomograms to individually estimate the survi...BACKGROUND There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas.AIM To develop comprehensive nomograms to individually estimate the survival outcome of patients with invasive intraductal papillary mucinous neoplasms of the pancreas.METHODS Data of 1219 patients with invasive intraductal papillary mucinous neoplasms after resection were extracted from the Surveillance,Epidemiology,and End Results database,and randomly divided into the training(n=853)and the validation(n=366)cohorts.Based on the Cox regression model,nomograms were constructed to predict overall survival and cancer-specific survival for an individual patient.The performance of the nomograms was measured according to discrimination,calibration,and clinical utility.Moreover,we compared the predictive accuracy of the nomograms with that of the traditional staging system.RESULTS In the training cohort,age,marital status,histological type,T stage,N stage,M stage,and chemotherapy were selected to construct nomograms.Compared with the American Joint Committee on Cancer 7th staging system,the nomograms were generally more discriminative.The nomograms passed the calibration steps by showing high consistency between actual probability and nomogram prediction.Categorial net classification improvements and integrated discrimination improvements suggested that the predictive accuracy of the nomograms exceeded that of the American Joint Committee on Cancer staging system.With respect to decision curve analyses,the nomograms exhibited more preferable net benefit gains than the staging system across a wide range of threshold probabilities.CONCLUSION The nomograms show improved predictive accuracy,discrimination capability,and clinical utility,which can be used as reliable tools for risk classification and treatment recommendations.展开更多
To reduce treatment-related side effects in low-risk prostate cancer(PCa),both focal therapy and deferred treatments,including active surveillance(AS)and watchful waiting(WW),are worth considering over radical prostat...To reduce treatment-related side effects in low-risk prostate cancer(PCa),both focal therapy and deferred treatments,including active surveillance(AS)and watchful waiting(WW),are worth considering over radical prostatectomy(RP).Therefore,this study aimed to compare long-term survival outcomes between focal therapy and AS/WW.Data were obtained and analyzed from the Surveillance,Epidemiology,and End Results(SEER)database.Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included.Focal therapy included cryotherapy and laser ablation.Multivariate Cox proportional hazards models were used to compare overall mortality(OM)and cancer-specific mortality(CSM)between AS/WW and focal therapy,and propensity score matching(PSM)was performed to reduce the influence of bias and unmeasured confounders.A total of 19292 patients with low-risk PCa were included in this study.In multivariate Cox proportional hazards model analysis,the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW(hazard ratio[HR]=1.35,95%confidence interval[CI]:1.02–1.79,P=0.037),whereas no significant difference was found in CSM(HR=0.98,95%CI:0.23–4.11,P=0.977).After PSM,the OM and CSM of focal therapy and AS/WW showed no significant differences(HR=1.26,95%CI:0.92–1.74,P=0.149;and HR=1.26,95%CI:0.24–6.51,P=0.782,respectively).For patients with low-risk PCa,focal therapy was no match for AS/WW in decreasing OM,suggesting that AS/WW could bring more overall survival benefits.展开更多
BACKGROUND There is no unified standard to predict postoperative survival in patients with tongue squamous cell carcinoma(TSCC),hence the urgency to develop a model to accurately predict the prognosis of these patient...BACKGROUND There is no unified standard to predict postoperative survival in patients with tongue squamous cell carcinoma(TSCC),hence the urgency to develop a model to accurately predict the prognosis of these patients.AIM To develop and validate nomograms for predicting overall survival(OS)and cancer-specific survival(CSS)of patients with TSCC.METHODS A cohort of 3454 patients with TSCC from the Surveillance,Epidemiology,and End Results(SEER)database was used to develop nomograms;another independent cohort of 203 patients with TSCC from the Department of Oral and Maxillofacial Surgery,First Affiliated Hospital of Zhejiang University School of Medicine,was used for external validation.Univariate and multivariate analyses were performed to identify useful variables for the development of nomograms.The calibration curve,area under the receiver operating characteristic curve(AUC)analysis,concordance index(C-index),net reclassification index(NRI),and decision curve analysis(DCA)were used to assess the calibration,discrimination ability,and clinical utility of the nomograms.RESULTS Eight variables were selected and used to develop nomograms for patients with TSCC.The Cindex(0.741 and 0.757 for OS and CSS in the training cohort and 0.800 and 0.830 in the validation cohort,respectively)and AUC indicated that the discrimination abilities of these nomograms were acceptable.The calibration curves of OS and CSS indicated that the predicted and actual values were consistent in both the training and validation cohorts.The NRI values(training cohort:0.493 and 0.482 for 3-and 5-year OS and 0.424 and 0.402 for 3-and 5-year CSS;validation cohort:0.635 and 0.750 for 3-and 5-year OS and 0.354 and 0.608 for 3-and 5-year CSS,respectively)and DCA results indicated that the nomograms were significantly better than the tumor-node-metastasis staging system in predicting the prognosis of patients with TSCC.CONCLUSION Our nomograms can accurately predict patient prognoses and assist clinicians in improving decision-making concerning patients with TSCC in clinical practice.展开更多
Prostate cancer(PCa)is the second-most common cancer among men.Both active surveillance or watchful waiting(AS/WW)and focal laser ablation(FLA)can avoid the complications caused by radical treatment.How to make the ch...Prostate cancer(PCa)is the second-most common cancer among men.Both active surveillance or watchful waiting(AS/WW)and focal laser ablation(FLA)can avoid the complications caused by radical treatment.How to make the choice between these options in clinical practice needs further study.Therefore,this study aims to compare and analyze their effects based on overall survival(OS)and cancer-specific survival(CSS)to obtain better long-term benefits.We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010–2016.Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups.To eliminate bias,this study applied a series of sensitivity analyses.Moreover,Kaplan–Meier curves were plotted to obtain survival status.A total of 18841 patients with low-risk PCa were included,with a median of 36-month follow-up.According to the multivariate Cox proportional hazard regression,the FLA group presented inferior survival benefits in OS than the AS/WW group(hazard ratio[HR]:2.13,95%confidence interval[CI]:1.37–3.33,P<0.05).After adjusting for confounders,the result persisted(HR:1.69,95%CI:1.02–2.81,P<0.05).According to the results of the sensitivity analysis,the inverse probability of the treatment weighing model indicated the same result in OS.In conclusion,AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment.Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa.More relevant researches and data will be needed for further clarity.展开更多
Background: The objective of this study was to evaluate the impact of radical prostatectomy on carcinosarcoma of the prostate. Methods: Patients diagnosed with carcinosarcoma of the prostate from 1977 through 2007 wer...Background: The objective of this study was to evaluate the impact of radical prostatectomy on carcinosarcoma of the prostate. Methods: Patients diagnosed with carcinosarcoma of the prostate from 1977 through 2007 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Outcomes were examined with Kaplan-Meier survival analysis and Cox models. The association between clinical and demographic characteristics and survival of carcinosarcoma of the prostate was examined. Results: A total of fifty-four cases of histology confirmed carcinosarcoma of the prostate were identified. Median age of the patients was 74 years (range 28 - 94). Of the patients with a known tumor stage, all but one patient had a locally advanced or distant stage;all of the patients with known histology grade had poorly or undifferentiated histology. Twenty (37%) patients underwent transurethral resection only and Fourteen (25.9%) patients underwent radical prostatectomy. Eight (14%) patients received radiation therapy in combination with surgery. The median cancer specific survival was 16 months (95% CI 0 - 32 months). 1-, 3-, and 5- year cancer specific survival rate were 55.1%, 32.3% and 21.1%. In a multivariate analysis, radical prostatectomy was found to be a significant prognostic factor for cancer-specific survival. Conclusions: Carcinosarcoma of the prostate commonly occurs in older patients and associated with aggressive disease and poor prognosis. Radical prostatectomy is the only treatment modality that significantly improves survival. Emphasis on early diagnosis and detection and multimodality therapy of this disease is needed to improve the outcome for patients with this malignancy.展开更多
Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how ...Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.展开更多
Background:Hepatocellular carcinoma(HCC)with portal vein invasion(PVI)is considered an advanced stage with a poor prognosis.Although current guidelines recommend systemic treatment for HCC with PVI,surgical resection ...Background:Hepatocellular carcinoma(HCC)with portal vein invasion(PVI)is considered an advanced stage with a poor prognosis.Although current guidelines recommend systemic treatment for HCC with PVI,surgical resection could produce acceptable outcomes in selected patients.This study aimed to identify the clinical significance of surgical resection for HCC with PVI patients using a large-scale nationwide registry.Methods:This retrospective,multicenter,observational cohort analyzed data from the Korean Primary Liver Cancer Registry.A total of 16,781 patients who were newly diagnosed with HCC between 2008 and 2018 were enrolled in this study.Patients with worse Child-Turcotte-Pugh scores(≥7)or performance status(≥2)were excluded.Among them,998 patients who received treatment for HCC with PVI were included in the analysis and were divided into two groups:resection group of 151(15.1%)and palliative group of 847(84.9%)who received transarterial and systemic therapy according to the treatment intent.After matching the number and size of the tumors and model for end-stage liver disease(MELD)score between the groups,the final study cohort for analysis comprised 151(26.6%)patients in the resection group and 417(73.4%)in the palliative group.The primary endpoints were overall survival(OS)and cancer-specific survival(CSS).Results:The number and maximum size of HCC did not differ between the resection and palliative groups after matching[1(range,1-5)vs.1(range,1-6),P=0.11 and 5.5(range,1.2-20.6)vs.6.0(range,1.0-20.5)cm,P=0.24,respectively].Tumor markers,including alpha-fetoprotein(AFP)and protein induced by vitamin K absence or antagonist-II(PIVKA-II),also did not differ between the groups(P=0.29 and P=0.36,respectively).The 5-year OS and CSS rates of the resection and palliative groups were 44.8%and 17.4%(P<0.001)and 47.7%and 18.6%(P<0.001),respectively.Multivariate analysis showed that palliative treatment intent was the most significant risk factor for OS and CSS[odds ratio(OR)=2.24;95%confidence interval(CI):1.66-3.02;P<0.001 and OR=2.29;95%CI:1.68-3.12;P<0.001,respectively].Conclusions:Surgical resection could significantly improve OS and CSS in selected HCC with PVI patients who have preserved liver function and performance status.展开更多
Purpose To construct an effective prognostic nomogram for patients with clinically localized Acral lentiginous mela-noma(ALM).Methods This retrospective study included ALM patients from the Surveillance,Epidemiology,a...Purpose To construct an effective prognostic nomogram for patients with clinically localized Acral lentiginous mela-noma(ALM).Methods This retrospective study included ALM patients from the Surveillance,Epidemiology,and End Results(SEER)database from 2004–2015.The 1686 cases were divided into the training and internal validation cohorts at a ratio of 7:3.The Cox regression analyses were performed to select risk factors for the nomogram.The performances of the nomogram were evaluated using the concordance index(C-index),area under receiver operating characteristic curve(AUC),and calibration plots,and validated in an external multicenter cohort.Results Age,gender,race,and stage were significantly associated with overall survival(OS),with a C-index of 0.727 and 0.722 in the training and internal validation groups,respectively.The AUC of 2-,4-,and 6 years were higher than or equal to 0.75.Age,gender,race,site,and stage were related to ALM patients’CSS which have better C-index of 0.791 and 0.774 in the training and internal validation set.The AUC of 2-,4-,and 6-were higher than or equal to 0.80.Both survival calibration curves of 2-,4,and 6-year OS and CSS brought out a good consistency.The external multicenter cohort authenticated the value of the nomogram of OS,with a C-index of 0.657 and an AUC of 0.67,0.72,and 0.65 at 2,4,and 6 years.Good consistency was also observed.Conclusion A prognostic nomogram was established and validated to help predict the survival of ALM patients and guide individualized treatment strategies.展开更多
Breast cancer-specific gene 1 (BCSG1), also referred as synuclein γ, was originally iso-lated from a human breast cancer cDNA library and the protein is mainly localized to presynaptic terminals in the nervous system...Breast cancer-specific gene 1 (BCSG1), also referred as synuclein γ, was originally iso-lated from a human breast cancer cDNA library and the protein is mainly localized to presynaptic terminals in the nervous system. BCSG1 is not expressed in normal or benign breast lesions, but expressed at an extremely high level in the vast majority of the advanced staged breast carcinomas and ovarian carcinomas. Overexpression of BCSG1 in cancer cells led to significant increase in cell proliferation, motility and invasiveness, and metastasis. To elucidate the molecular mechanism and regulation for abnormal transcription of BCSG1, a variety of BCSG1 promoter luciferase reporters were constructed including 3′ end deleted sequences, Sp1 deleted, and activator protein-1 (AP1) domains mutated. Transient transfection assay was used to detect the transcriptional activation of BCSG1 promoters. Results showed that the Sp1 sequence in 5′-flanking region was involved in the basal transcriptional activities of BCSG1 without cell-type specificity. In comparison to pGL3-1249, the reporter activities of pGL3-1553 in BCSG1-negative MCF-7 cells and pGL3-1759 in HepG2 cells were notably decreased. Mutations at AP1 sites in BCSG1 intron 1 significantly reduced the promoter ac-tivity in all cell lines. Transcription factors, c-jun, c-fos and cyclin AMP-responsive element binding (CREB) protein, could markedly enhance the promoter activities. Thus, our results suggest that the abnormal expression of BCSG1 in breast cancer cells is likely regulated by multiple mechanisms. The 5′ flanking region of BCSG1 provides the basal transcriptional activity without cell type specificity. A critical promoter element involved in abnormal expression of BCSG1 presents in the first exon. The cell type specificity of BCSG1 transcription is probably affected through intronic cis-regulatory se-quences. AP1 domains in the first intron play an important role in control of BCSG1 transcription.展开更多
Background:Asians are diagnosed with breast cancer at a younger age than Caucasians are.We studied the effect of age on locoregional recurrence and the survival of Asian breast cancer patients treated with breast-cons...Background:Asians are diagnosed with breast cancer at a younger age than Caucasians are.We studied the effect of age on locoregional recurrence and the survival of Asian breast cancer patients treated with breast-conserving therapy.Methods:Medical records of 2492 patients treated with breast-conserving therapy between 1989 and 2012 were reviewed.The Kaplan-Meier method was used to estimate locoregional recurrence,breast cancer-free survival,and breast cancer-specific survival rates.These rates were then compared using log-rank tests.Outcomes and age were modeled by Cox proportional hazards.Fractional polynomials were then used to test for non-linear relationships between age and outcomes.Results:Patients≤40 years old were more likely to have locoregional recurrence than were older patients(Hazard ratio[HR]=2.32,P<0.001).Locoregional recurrence rates decreased year-on-year by 4%for patients with luminal-type breast cancers,compared with 8%for those with triple-negative cancers.Similarly,breast cancer-free survival rates increased year-on-year by 4%versus 8%for luminal-type and triple-negative cancers,respectively.Breast cancer-spe-cific survival rates increased with age by 5%year-on-year.Both breast cancer-free survival and breast cancer-specific survival rates in patients with luminal cancers exhibited a non-linear(“L-shaped”)relationship-where decreasing age at presentation was associated with escalating risks of relapse and death.The influence of age on overall survival was confounded by competing non-cancer deaths in older women,resulting in a“U-shaped”relationship.Conclusions:Young Asian breast cancer patients have a continuous year-on-year increase in rates of disease relapse and cancer deaths compared with older patients with no apparent threshold.展开更多
Background No well-performing nomogram has been developed specifically to predict individual-patient cancer-specific survival(CSS)and overall survival(OS)among patients with resectable colorectal liver metastasis(CRLM...Background No well-performing nomogram has been developed specifically to predict individual-patient cancer-specific survival(CSS)and overall survival(OS)among patients with resectable colorectal liver metastasis(CRLM)who undergo simultaneous resection of primary and hepatic lesions without neoadjuvant chemotherapy(NAC).We aim to investigate the prognosis of patients with resectable CRLM undergoing simultaneous resection of primary and hepatic lesions without NAC.Methods Data of patients with CRLM in the Surveillance,Epidemiology and End Results Program(cohort,n=225)were collected as the training set,and data of patients with CRLM treated at the National Cancer Center(cohort,n=180)were collected as the validation set.The prognostic value of the clinicopathological parameters in the training cohort was assessed using Kaplan‒Meier curves and univariate and multivariate Cox proportional hazards models,and OS and CSS nomograms integrated with the prognostic variables were constructed.Calibration analyses,receiver operating characteristic(ROC)curves,and decision curve analyses(DCAs)were then performed to evaluate the performance of the nomograms.Results There was no collinearity among the collected variables.Three factors were associated with OS and CSS:the pretreatment carcinoembryonic antigen(CEA)concentration,pathologic N(pN)stage,and adjuvant chemotherapy(each p<0.05).OS and CSS nomograms were constructed using these three parameters.The calibration plots revealed favorable agreement between the predicted and observed outcomes.The areas under the ROC curves were approximately 0.7.The DCA plots revealed that both nomograms had satisfactory clinical benefits.The ROC curves and DCAs also confirmed that the nomogram surpassed the tumor,node,and metastasis staging system.Conclusion The herein-described nomograms containing the pretreatment CEA concentration,pN stage,and adjuvant chemotherapy may be effective models for predicting postoperative survival in patients with CRLM.展开更多
基金supported by grants from National Natural Science Foundation of China(No.81702708)Natural Science Foundation of Hunan Province(No.2018JJ3862,No.2017JJ2392,and No.2019JJ50979)+1 种基金Scientific Research Project of Hunan Provincial Health Commission(No.B20180054)Changsha Science and Technology Project(No.kq1706072).
文摘The use of the traditional American Joint Committee on Cancer(AJCC)staging system alone has limitations in predicting the survival of gingiva squamous cell carcinoma(GSCC)patients.We aimed to establish a comprehensive prognostic nomogram with a prognostic value similar to the AJCC system.Methods:Patients were identified from SEER database.Variables were selected by a backward stepwise selection method in a Cox regression model.A nomogram was used to predict cancer-specific survival rates for 3,5 and 10 years in patients with GSCC.Several basic features of model validation were used to evaluate the performance of the survival model:consistency index(C-index),receiver operating characteristic(ROC)curve,calibration chart,net weight classification improvement(NRI),comprehensive discriminant improvement(IDI)and decision curve analysis(DCA).Results:Multivariate analyses revealed that age,race,marital status,insurance,AJCC stage,pathology grade and surgery were risk factors for survival.In particular,the C-index,the area under the ROC curve(AUC)and the calibration plots showed good performance of the nomogram.Compared to the AJCC system,NRI and IDI showed that the nomogram has improved performance.Finally,the nomogram's 3-year and 5-year and 10-year DCA curves yield net benefits higher than traditional AJCC,whether training set or a validation set.Conclusion:We developed and validated the first GSCC prognosis nomogram,which has a better prognostic value than the separate AJCC staging system.Overall,the nomogram of this study is a valuable tool for clinical practice to consult patients and understand their risk for the next 3,5 and 10 years.
文摘Objectives:This study aimed to test the association between of type and number of D'Amico high-risk criteria(DHRCs)with cancer-specific mortality(CSM)in high-risk prostate cancer patients treated with radical prostatectomy.Materials and methods:In the Surveillance,Epidemiology,and End Results database(2004–2016),we identified 31,281 radical prostatectomy patients with at least 1 DHRC,namely,prostate-specific antigen(PSA)>20 ng/mL(hrPSA),biopsy Gleason Grade Group(hrGGG)score of 4 and 5,or clinical tumor stage≥T3(hrcT).Multivariable Cox regression models and competing risks regression models(adjusting for other cause mortality)tested the association between DHRCs and 5-year CSM.Results:Of 31,281 patients,14,394(67%)exclusively harbored hrGGG,3189(15%)harbored hrPSA,and 1781(8.2%)harbored hrcT.Only 2132 patients(6.8%)harbored a combination of the 2 DHRCs,and 138(0.6%)had all 3 DHRCs.Five-year CSMrates ranged from 0.9%to 3.0%when any individual DHRC was present(hrcT,hrPSA,and hrGGG,in that order),1.6%to 5.9%when 2 DHRCs were present(hrPSA-hrcT,hrcT-hrGGG,and hrPSA-hrGGG,in that order),and 8.1%when all 3 DHRCs were present.Cox regression models and competing risks regression confirmed the independent predictor status of DHRCs for 5-year CSM that was observed in univariable analyses,with hazard ratios from 1.00 to 2.83 for 1 DHRC,2.35 to 5.88 for combinations of 2 DHRCs,and 7.13 for all 3 DHRCs.Conclusions:Within individual DHRCs,hrcT and hrPSA exhibited weaker effects than hrGGG did.Moreover,a dose-response effect was identified according to the number of DHRCs.Accordingly,the type and number of DHRCs allow further risk stratification within the high-risk subgroup.
文摘Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.
基金supported by the National Natural Science Foundation of China(Nos.21877030,21735002,21778016).
文摘Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer cells.However,the conventional ATP biosensing strat-egy is often limited by the undesired on-target off-tumor interference.Here,we reported a novel strategy to design enzymatically controlled DNA tetrahedron nanoprobes(En-DT)for biosensing and imaging ATP in tumor cells.The En-DT was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on the DNA tetrahedron.The En-DT could be catalytically activated by apurinic/apyrimidinic endonuclease 1(APE1)in cancer cells,but they did not respond to ATP in normal cells,thereby enabling cancer-specific ATP biosensing and imaging in vitro and in vivo with improved tumor specificity.This strategy would facilitate the precise detection of a broad range of biomarker in tumors and may promote the development of smart probes for cancer diagnosis.
文摘Background and Objective The effectiveness of radiofrequency ablation(RFA)in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma(HCC)measuring 5 cm or less remains uncertain.This study was designed to elucidate the impact of RFA therapy on the survival outcomes of these patients and to construct a prognostic model for patients following RFA.Methods This study was performed using the Surveillance,Epidemiology,and End Results(SEER)database from 2004 to 2017,focusing on patients diagnosed with a solitary HCC lesion≤5 cm in size.We compared the overall survival(OS)and cancer-specific survival(CSS)rates of these patients with those of patients who received hepatectomy,radiotherapy,or chemotherapy or who were part of a blank control group.To enhance the reliability of our findings,we employed stabilized inverse probability treatment weighting(sIPTW)and stratified analyses.Additionally,we conducted a Cox regression analysis to identify prognostic factors.XGBoost models were developed to predict 1-,3-,and 5-year CSS.The XGBoost models were evaluated via receiver operating characteristic(ROC)curves,calibration plots,decision curve analysis(DCA)curves and so on.Results Regardless of whether the data were unadjusted or adjusted for the use of sIPTWs,the 5-year OS(46.7%)and CSS(58.9%)rates were greater in the RFA group than in the radiotherapy(27.1%/35.8%),chemotherapy(32.9%/43.7%),and blank control(18.6%/30.7%)groups,but these rates were lower than those in the hepatectomy group(69.4%/78.9%).Stratified analysis based on age and cirrhosis status revealed that RFA and hepatectomy yielded similar OS and CSS outcomes for patients with cirrhosis aged over 65 years.Age,race,marital status,grade,cirrhosis status,tumor size,and AFP level were selected to construct the XGBoost models based on the training cohort.The areas under the curve(AUCs)for 1,3,and 5 years in the validation cohort were 0.88,0.81,and 0.79,respectively.Calibration plots further demonstrated the consistency between the predicted and actual values in both the training and validation cohorts.Conclusion RFA can improve the survival of patients diagnosed with a solitary HCC lesion≤5 cm.In certain clinical scenarios,RFA achieves survival outcomes comparable to those of hepatectomy.The XGBoost models developed in this study performed admirably in predicting the CSS of patients with solitary HCC tumors smaller than 5 cm following RFA.
文摘Objective: To explore the prognostic value of log odds of positive lymph nodes (LODDS) in patients with gastroenteropancreatic neuroendocrine tumors (GEPNET) and to develop nomograms based on LODDS for predicting 1-year, 3-year, and 5-year overall survival (OS) and cancer-specific survival (CSS). Methods: This retrospective cohort study was based on the Surveillance, Epidemiology, and End Results (SEER) Program. Demographic data, clinical data, and survival status were extracted, with endpoints of OS and CSS. Multivariate Cox proportional hazards regression analysis assessed predictors associated with OS and CSS, with hazard ratios (HRs) and 95% confidence intervals (CIs) evaluated. Nomogram performance was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC). Results: A total of 1,673 patients were included and divided into a training set (n = 1,172) and a testing set (n = 501). Multivariate Cox proportional hazards regression analyses identified LODDS as an independent prognostic factor for OS (HR = 1.79, 95% CI: 1.44-2.24) and CSS (HR = 1.81, 95% CI: 1.41-2.31). The OS and CSS nomograms, developed from multivariate Cox regression analyses, showed good performance, with AUCs of 0.858, 0.878, and 0.852 for predicting 1-year, 3-year, and 5-year OS, and AUCs of 0.859, 0.887, and 0.865 for 1-year, 3-year, and 5-year CSS in the testing set. The nomograms are accessible online (OS: https://zhmte.shinyapps.io/DynNomapp/;CSS: https:// zhmty.shinyapps.io/DynNomapp/). Conclusions: LODDS serves as an independent prognostic factor in GEPNET. Online nomograms based on LODDS demonstrated effective performance in predicting OS and CSS in GEPNET patients, providing a convenient tool for clinical application.
基金supported by grants from the National Natural Science Foundation of China(No.81672353 and 81871954)。
文摘Objective:To validate the 8 th edition of the American Joint Committee on Cancer(AJCC)staging system for pancreatic ductal adenocarcinoma(PDAC)in a Chinese cohort of radically resected patients and to develop a refined staging system for PDAC.Methods:Data were collected from the China Pancreas Data Center(CPDC)for patients with resected PDAC in 2016 and 2017,and cancer-specific survival(CSS)was evaluated using the Kaplan-Meier method and log-rank test.Univariate and multivariate analyses based on Cox regression were performed to identify prognostic factors.The recursive partitioning analysis(RPA),Kaplan-Meier method,and log-rank test were performed on the training dataset to generate a proposed modification for the 8 th TNM staging system utilizing the preoperative carbohydrate antigen(CA)19-9 level.Validation was performed for both staging systems in the validation cohort.Results:A total of 1,676 PDAC patients were retrieved,and the median CSS was significantly different between the 8 th TNM groupings,with no significant difference in survival between stage IB and IIA.The analysis of T and N stages demonstrated a better prognostic value in the N category.Multivariate analysis showed that the preoperative serum CA19-9 level was the strongest prognostic indicator among all the independent risk factors.All patients with CA19-9>500 U/mL had similar survival,and we proposed a new staging system by combining IB and IIA and stratifying all patients with high CA19-9 into stage III.The modified staging system had a better performance for predicting CSS than the 8 th AJCC staging scheme.Conclusions:The 8 th AJCC staging system for PDAC is suitable for a Chinese cohort of resected patients,and the N category has a better prognostic value than the T category.Our modified staging system has superior accuracy in predicting survival than the 8 th AJCC TNM staging system.
基金provided by the National Basic Research Program of China (973 Program) (No.2015CB554001,JW )the National Natural Science Foundation of China (No.81472257,YL+6 种基金No.81201920,YLNo.81502022,XW )the Natural Science Foundation of Guangdong Province (No.S2013010013607,YL)the Science and Technology Program of Guangzhou (No.201506010099,YL)the Fundamental Research Funds for the Central Universities (Sun Yat-sen University) (No.2015ykzd10,YLNo.13ykpy37,YL)Wu Jieping Medical Foundation (320675015173 HY)
文摘Background:Several studies suggested that hypertension is positively related to cancer incidence and mortality.In this study,we investigated the association between perioperative blood pressure(BP) and long?term survival out?comes in patients with rectal cancer.Methods:This study included a cohort of 358 patients with stages I–III rectal cancer who underwent a curative resection between June 2007 and June 2011.Both pre? and postoperative BPs were measured,by which patients were grouped(low BP:<120/80 mm Hg;high BP:ints were di≥120/80 mm Hg).The survival outcomes were compared between these two groups.The primary endposease?free survival(DFS) and cancer?specific survival(CSS).Results:Univariate analysis showed that patients with high preoperative systolic BP had lower 3?year DFS(67.2% vs.82.1%,P = 0.041) and CSS rates(81.9% vs.94.8%,P = 0.003) than patients with low preoperative systolic BP,and the associations remained significant in the Cox multivariate analysis,with the adjusted hazard ratios equal to 1.97 [95% confidence interval(CI) = 1.08–3.60,P = 0.028] and 2.85(95% CI = 1.00–8.25,P = 0.050),respectively.Similarly,in postoperative evaluation,patients with high systolic BP had significantly lower 3?year CSS rates than those with low systolic BP(78.3% vs.88.9%,P = 0.032) in univariate analysis.Moreover,high pre? and/or postoperative systolic BP presented as risk factors for CSS in the subgroups of patients who did not have a history of hypertension,with and/or without perioperative administration of antihypertensive drugs.Conclusions:High preoperative systolic BP was an independent risk factor for both CSS and DFS rates,and high postoperative systolic BP was significantly associated with a low CSS rate in rectal cancer patients.Additionally,our results suggest that rectal cancer patients may get survival benefit from BP control in perioperative care.However,further studies should be conducted to determine the association between BP and CSS and targets of BP control.
基金Supported by National Natural Science Foundation of China,No.81702270the Natural Science Foundation of Guangdong,No.2015A030313827The Affiliated Hospital of Guangdong Medical University Clinical Research Program,No.LCYJ2018C012
文摘BACKGROUND There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas.AIM To develop comprehensive nomograms to individually estimate the survival outcome of patients with invasive intraductal papillary mucinous neoplasms of the pancreas.METHODS Data of 1219 patients with invasive intraductal papillary mucinous neoplasms after resection were extracted from the Surveillance,Epidemiology,and End Results database,and randomly divided into the training(n=853)and the validation(n=366)cohorts.Based on the Cox regression model,nomograms were constructed to predict overall survival and cancer-specific survival for an individual patient.The performance of the nomograms was measured according to discrimination,calibration,and clinical utility.Moreover,we compared the predictive accuracy of the nomograms with that of the traditional staging system.RESULTS In the training cohort,age,marital status,histological type,T stage,N stage,M stage,and chemotherapy were selected to construct nomograms.Compared with the American Joint Committee on Cancer 7th staging system,the nomograms were generally more discriminative.The nomograms passed the calibration steps by showing high consistency between actual probability and nomogram prediction.Categorial net classification improvements and integrated discrimination improvements suggested that the predictive accuracy of the nomograms exceeded that of the American Joint Committee on Cancer staging system.With respect to decision curve analyses,the nomograms exhibited more preferable net benefit gains than the staging system across a wide range of threshold probabilities.CONCLUSION The nomograms show improved predictive accuracy,discrimination capability,and clinical utility,which can be used as reliable tools for risk classification and treatment recommendations.
基金supported by the National Key Research and Development Program of China(SQ2017YFSF090096)the National Natural Science Foundation of China(81770756)the Sichuan Science and Technology Program(2017HH0063)。
文摘To reduce treatment-related side effects in low-risk prostate cancer(PCa),both focal therapy and deferred treatments,including active surveillance(AS)and watchful waiting(WW),are worth considering over radical prostatectomy(RP).Therefore,this study aimed to compare long-term survival outcomes between focal therapy and AS/WW.Data were obtained and analyzed from the Surveillance,Epidemiology,and End Results(SEER)database.Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included.Focal therapy included cryotherapy and laser ablation.Multivariate Cox proportional hazards models were used to compare overall mortality(OM)and cancer-specific mortality(CSM)between AS/WW and focal therapy,and propensity score matching(PSM)was performed to reduce the influence of bias and unmeasured confounders.A total of 19292 patients with low-risk PCa were included in this study.In multivariate Cox proportional hazards model analysis,the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW(hazard ratio[HR]=1.35,95%confidence interval[CI]:1.02–1.79,P=0.037),whereas no significant difference was found in CSM(HR=0.98,95%CI:0.23–4.11,P=0.977).After PSM,the OM and CSM of focal therapy and AS/WW showed no significant differences(HR=1.26,95%CI:0.92–1.74,P=0.149;and HR=1.26,95%CI:0.24–6.51,P=0.782,respectively).For patients with low-risk PCa,focal therapy was no match for AS/WW in decreasing OM,suggesting that AS/WW could bring more overall survival benefits.
文摘BACKGROUND There is no unified standard to predict postoperative survival in patients with tongue squamous cell carcinoma(TSCC),hence the urgency to develop a model to accurately predict the prognosis of these patients.AIM To develop and validate nomograms for predicting overall survival(OS)and cancer-specific survival(CSS)of patients with TSCC.METHODS A cohort of 3454 patients with TSCC from the Surveillance,Epidemiology,and End Results(SEER)database was used to develop nomograms;another independent cohort of 203 patients with TSCC from the Department of Oral and Maxillofacial Surgery,First Affiliated Hospital of Zhejiang University School of Medicine,was used for external validation.Univariate and multivariate analyses were performed to identify useful variables for the development of nomograms.The calibration curve,area under the receiver operating characteristic curve(AUC)analysis,concordance index(C-index),net reclassification index(NRI),and decision curve analysis(DCA)were used to assess the calibration,discrimination ability,and clinical utility of the nomograms.RESULTS Eight variables were selected and used to develop nomograms for patients with TSCC.The Cindex(0.741 and 0.757 for OS and CSS in the training cohort and 0.800 and 0.830 in the validation cohort,respectively)and AUC indicated that the discrimination abilities of these nomograms were acceptable.The calibration curves of OS and CSS indicated that the predicted and actual values were consistent in both the training and validation cohorts.The NRI values(training cohort:0.493 and 0.482 for 3-and 5-year OS and 0.424 and 0.402 for 3-and 5-year CSS;validation cohort:0.635 and 0.750 for 3-and 5-year OS and 0.354 and 0.608 for 3-and 5-year CSS,respectively)and DCA results indicated that the nomograms were significantly better than the tumor-node-metastasis staging system in predicting the prognosis of patients with TSCC.CONCLUSION Our nomograms can accurately predict patient prognoses and assist clinicians in improving decision-making concerning patients with TSCC in clinical practice.
文摘Prostate cancer(PCa)is the second-most common cancer among men.Both active surveillance or watchful waiting(AS/WW)and focal laser ablation(FLA)can avoid the complications caused by radical treatment.How to make the choice between these options in clinical practice needs further study.Therefore,this study aims to compare and analyze their effects based on overall survival(OS)and cancer-specific survival(CSS)to obtain better long-term benefits.We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010–2016.Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups.To eliminate bias,this study applied a series of sensitivity analyses.Moreover,Kaplan–Meier curves were plotted to obtain survival status.A total of 18841 patients with low-risk PCa were included,with a median of 36-month follow-up.According to the multivariate Cox proportional hazard regression,the FLA group presented inferior survival benefits in OS than the AS/WW group(hazard ratio[HR]:2.13,95%confidence interval[CI]:1.37–3.33,P<0.05).After adjusting for confounders,the result persisted(HR:1.69,95%CI:1.02–2.81,P<0.05).According to the results of the sensitivity analysis,the inverse probability of the treatment weighing model indicated the same result in OS.In conclusion,AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment.Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa.More relevant researches and data will be needed for further clarity.
文摘Background: The objective of this study was to evaluate the impact of radical prostatectomy on carcinosarcoma of the prostate. Methods: Patients diagnosed with carcinosarcoma of the prostate from 1977 through 2007 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Outcomes were examined with Kaplan-Meier survival analysis and Cox models. The association between clinical and demographic characteristics and survival of carcinosarcoma of the prostate was examined. Results: A total of fifty-four cases of histology confirmed carcinosarcoma of the prostate were identified. Median age of the patients was 74 years (range 28 - 94). Of the patients with a known tumor stage, all but one patient had a locally advanced or distant stage;all of the patients with known histology grade had poorly or undifferentiated histology. Twenty (37%) patients underwent transurethral resection only and Fourteen (25.9%) patients underwent radical prostatectomy. Eight (14%) patients received radiation therapy in combination with surgery. The median cancer specific survival was 16 months (95% CI 0 - 32 months). 1-, 3-, and 5- year cancer specific survival rate were 55.1%, 32.3% and 21.1%. In a multivariate analysis, radical prostatectomy was found to be a significant prognostic factor for cancer-specific survival. Conclusions: Carcinosarcoma of the prostate commonly occurs in older patients and associated with aggressive disease and poor prognosis. Radical prostatectomy is the only treatment modality that significantly improves survival. Emphasis on early diagnosis and detection and multimodality therapy of this disease is needed to improve the outcome for patients with this malignancy.
基金funding from the National Science Foundation of China(31930016)the Peking-Tsinghua Center for Life Sciences+4 种基金ZW received funding from the State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases(2024KF00001)the National Science Foundation of China(82350119)CCW received funding from the Talent Introduction Funds from the Chinese Academy of Medical Science(2022-RC310-10)the National Science Foundation of China(32150005)the Research Funds from Health@InnoHK Program,launched by the Innovation Technology Commission of the Hong Kong Special Administrative Region.
文摘Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.
文摘Background:Hepatocellular carcinoma(HCC)with portal vein invasion(PVI)is considered an advanced stage with a poor prognosis.Although current guidelines recommend systemic treatment for HCC with PVI,surgical resection could produce acceptable outcomes in selected patients.This study aimed to identify the clinical significance of surgical resection for HCC with PVI patients using a large-scale nationwide registry.Methods:This retrospective,multicenter,observational cohort analyzed data from the Korean Primary Liver Cancer Registry.A total of 16,781 patients who were newly diagnosed with HCC between 2008 and 2018 were enrolled in this study.Patients with worse Child-Turcotte-Pugh scores(≥7)or performance status(≥2)were excluded.Among them,998 patients who received treatment for HCC with PVI were included in the analysis and were divided into two groups:resection group of 151(15.1%)and palliative group of 847(84.9%)who received transarterial and systemic therapy according to the treatment intent.After matching the number and size of the tumors and model for end-stage liver disease(MELD)score between the groups,the final study cohort for analysis comprised 151(26.6%)patients in the resection group and 417(73.4%)in the palliative group.The primary endpoints were overall survival(OS)and cancer-specific survival(CSS).Results:The number and maximum size of HCC did not differ between the resection and palliative groups after matching[1(range,1-5)vs.1(range,1-6),P=0.11 and 5.5(range,1.2-20.6)vs.6.0(range,1.0-20.5)cm,P=0.24,respectively].Tumor markers,including alpha-fetoprotein(AFP)and protein induced by vitamin K absence or antagonist-II(PIVKA-II),also did not differ between the groups(P=0.29 and P=0.36,respectively).The 5-year OS and CSS rates of the resection and palliative groups were 44.8%and 17.4%(P<0.001)and 47.7%and 18.6%(P<0.001),respectively.Multivariate analysis showed that palliative treatment intent was the most significant risk factor for OS and CSS[odds ratio(OR)=2.24;95%confidence interval(CI):1.66-3.02;P<0.001 and OR=2.29;95%CI:1.68-3.12;P<0.001,respectively].Conclusions:Surgical resection could significantly improve OS and CSS in selected HCC with PVI patients who have preserved liver function and performance status.
基金supported by the Shanghai Science and Technology Development Funds(19411951700 to Y.Chen)LinGang laboratory“Seeking Distinguished Young Scholars”project(LG-QS-202205-11 to W.Sun)the National Natural Science Foundation of China(81802636 to W.Sun).
文摘Purpose To construct an effective prognostic nomogram for patients with clinically localized Acral lentiginous mela-noma(ALM).Methods This retrospective study included ALM patients from the Surveillance,Epidemiology,and End Results(SEER)database from 2004–2015.The 1686 cases were divided into the training and internal validation cohorts at a ratio of 7:3.The Cox regression analyses were performed to select risk factors for the nomogram.The performances of the nomogram were evaluated using the concordance index(C-index),area under receiver operating characteristic curve(AUC),and calibration plots,and validated in an external multicenter cohort.Results Age,gender,race,and stage were significantly associated with overall survival(OS),with a C-index of 0.727 and 0.722 in the training and internal validation groups,respectively.The AUC of 2-,4-,and 6 years were higher than or equal to 0.75.Age,gender,race,site,and stage were related to ALM patients’CSS which have better C-index of 0.791 and 0.774 in the training and internal validation set.The AUC of 2-,4-,and 6-were higher than or equal to 0.80.Both survival calibration curves of 2-,4,and 6-year OS and CSS brought out a good consistency.The external multicenter cohort authenticated the value of the nomogram of OS,with a C-index of 0.657 and an AUC of 0.67,0.72,and 0.65 at 2,4,and 6 years.Good consistency was also observed.Conclusion A prognostic nomogram was established and validated to help predict the survival of ALM patients and guide individualized treatment strategies.
文摘Breast cancer-specific gene 1 (BCSG1), also referred as synuclein γ, was originally iso-lated from a human breast cancer cDNA library and the protein is mainly localized to presynaptic terminals in the nervous system. BCSG1 is not expressed in normal or benign breast lesions, but expressed at an extremely high level in the vast majority of the advanced staged breast carcinomas and ovarian carcinomas. Overexpression of BCSG1 in cancer cells led to significant increase in cell proliferation, motility and invasiveness, and metastasis. To elucidate the molecular mechanism and regulation for abnormal transcription of BCSG1, a variety of BCSG1 promoter luciferase reporters were constructed including 3′ end deleted sequences, Sp1 deleted, and activator protein-1 (AP1) domains mutated. Transient transfection assay was used to detect the transcriptional activation of BCSG1 promoters. Results showed that the Sp1 sequence in 5′-flanking region was involved in the basal transcriptional activities of BCSG1 without cell-type specificity. In comparison to pGL3-1249, the reporter activities of pGL3-1553 in BCSG1-negative MCF-7 cells and pGL3-1759 in HepG2 cells were notably decreased. Mutations at AP1 sites in BCSG1 intron 1 significantly reduced the promoter ac-tivity in all cell lines. Transcription factors, c-jun, c-fos and cyclin AMP-responsive element binding (CREB) protein, could markedly enhance the promoter activities. Thus, our results suggest that the abnormal expression of BCSG1 in breast cancer cells is likely regulated by multiple mechanisms. The 5′ flanking region of BCSG1 provides the basal transcriptional activity without cell type specificity. A critical promoter element involved in abnormal expression of BCSG1 presents in the first exon. The cell type specificity of BCSG1 transcription is probably affected through intronic cis-regulatory se-quences. AP1 domains in the first intron play an important role in control of BCSG1 transcription.
文摘Background:Asians are diagnosed with breast cancer at a younger age than Caucasians are.We studied the effect of age on locoregional recurrence and the survival of Asian breast cancer patients treated with breast-conserving therapy.Methods:Medical records of 2492 patients treated with breast-conserving therapy between 1989 and 2012 were reviewed.The Kaplan-Meier method was used to estimate locoregional recurrence,breast cancer-free survival,and breast cancer-specific survival rates.These rates were then compared using log-rank tests.Outcomes and age were modeled by Cox proportional hazards.Fractional polynomials were then used to test for non-linear relationships between age and outcomes.Results:Patients≤40 years old were more likely to have locoregional recurrence than were older patients(Hazard ratio[HR]=2.32,P<0.001).Locoregional recurrence rates decreased year-on-year by 4%for patients with luminal-type breast cancers,compared with 8%for those with triple-negative cancers.Similarly,breast cancer-free survival rates increased year-on-year by 4%versus 8%for luminal-type and triple-negative cancers,respectively.Breast cancer-spe-cific survival rates increased with age by 5%year-on-year.Both breast cancer-free survival and breast cancer-specific survival rates in patients with luminal cancers exhibited a non-linear(“L-shaped”)relationship-where decreasing age at presentation was associated with escalating risks of relapse and death.The influence of age on overall survival was confounded by competing non-cancer deaths in older women,resulting in a“U-shaped”relationship.Conclusions:Young Asian breast cancer patients have a continuous year-on-year increase in rates of disease relapse and cancer deaths compared with older patients with no apparent threshold.
基金National Natural Science Foundation of China,Grant/Award Number:81441070。
文摘Background No well-performing nomogram has been developed specifically to predict individual-patient cancer-specific survival(CSS)and overall survival(OS)among patients with resectable colorectal liver metastasis(CRLM)who undergo simultaneous resection of primary and hepatic lesions without neoadjuvant chemotherapy(NAC).We aim to investigate the prognosis of patients with resectable CRLM undergoing simultaneous resection of primary and hepatic lesions without NAC.Methods Data of patients with CRLM in the Surveillance,Epidemiology and End Results Program(cohort,n=225)were collected as the training set,and data of patients with CRLM treated at the National Cancer Center(cohort,n=180)were collected as the validation set.The prognostic value of the clinicopathological parameters in the training cohort was assessed using Kaplan‒Meier curves and univariate and multivariate Cox proportional hazards models,and OS and CSS nomograms integrated with the prognostic variables were constructed.Calibration analyses,receiver operating characteristic(ROC)curves,and decision curve analyses(DCAs)were then performed to evaluate the performance of the nomograms.Results There was no collinearity among the collected variables.Three factors were associated with OS and CSS:the pretreatment carcinoembryonic antigen(CEA)concentration,pathologic N(pN)stage,and adjuvant chemotherapy(each p<0.05).OS and CSS nomograms were constructed using these three parameters.The calibration plots revealed favorable agreement between the predicted and observed outcomes.The areas under the ROC curves were approximately 0.7.The DCA plots revealed that both nomograms had satisfactory clinical benefits.The ROC curves and DCAs also confirmed that the nomogram surpassed the tumor,node,and metastasis staging system.Conclusion The herein-described nomograms containing the pretreatment CEA concentration,pN stage,and adjuvant chemotherapy may be effective models for predicting postoperative survival in patients with CRLM.
