BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors...BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.AIM To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.METHODS A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study.The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer’s recommendations along with the normal gingival epithelium as a positive control.All the observations were recorded and Pearson’sχ²test with Fisher exact test was used for statistical analysis.RESULTS Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size.The majority of the patients were in advanced TNM stages(III and IV),and showed intense expression of MMP-9 and MMP-13.CONCLUSION The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness.Intense expression of MMP-9 and MMP-13,irrespective of histological grade of OSCC,correlates well with TNM stage.Consequently,it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors.The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques,hence enhancing the prognosis of patients diagnosed with OSCC.展开更多
Gastric cancer(GC)remains a leading cause of cancer mortality.While the extent of nodal involvement is a well-known prognostic factor,the specific entity of swollen lymph node metastasis(SLNM),bulky nodal tumor deposi...Gastric cancer(GC)remains a leading cause of cancer mortality.While the extent of nodal involvement is a well-known prognostic factor,the specific entity of swollen lymph node metastasis(SLNM),bulky nodal tumor deposits detectable radiologically or pathologically,has received little attention in staging.Recent data from a study by Cui et al demonstrated that SLNM is an independent predictor of very poor survival in GC.Through robust data and rigorous propensitymatched analyses,SLNM emerged not merely as an anatomical finding but as an independent predictor of poor prognosis,even among patients undergoing curative resection.As precision oncology advances,the findings by Cui et al urge a fundamental rethinking of how SLNM is incorporated into clinical decisionmaking for GC management.In this editorial,we critically examine the prognostic significance of SLNM,challenge its omission from traditional staging frameworks,and advocate for its formal integration into preoperative risk stratification and treatment planning.Recognizing SLNM at diagnosis could unlock intensified neoadjuvant therapy strategies and optimize outcomes for a historically high-risk patient subgroup.展开更多
Accurate preoperative prediction of lymph node metastasis is crucial for developing clinical management strategies for patients with esophageal cancer.In this letter,we present our insights and opinions on a new nomog...Accurate preoperative prediction of lymph node metastasis is crucial for developing clinical management strategies for patients with esophageal cancer.In this letter,we present our insights and opinions on a new nomogram proposed by Xu et al.Although this research has great potential,there are still concerns re-garding the small sample size,limited consideration of biological complexity,subjective image segmentation,incomplete image feature extraction and statistical analyses.Furthermore,we discuss how to achieve more robust and accurate predictive performance in future research.展开更多
BACKGROUND Tissue hardness is closely related to disease pathophysiology.Shear-wave ela-stography(SWE)is a simple and noninvasive ultrasound technique that has been used to evaluate the presence of lymph node metastas...BACKGROUND Tissue hardness is closely related to disease pathophysiology.Shear-wave ela-stography(SWE)is a simple and noninvasive ultrasound technique that has been used to evaluate the presence of lymph node metastases and differentiate between benign and malignant tumors.AIM To investigate SWE usefulness in measuring lymph node hardness to predict metastasis presence or absence in surgically removed lymph nodes.METHODS This observational study obtained data from patients who underwent surgery for esophageal or gastric cancer at Nippon Medical School Hospital.The hardness of the surgically removed lymph nodes was measured using SWE.The lymph nodes with hardness values≥2.2 m/s were considered clinically positive for metastasis,whereas those with lower hardness values were considered clinically negative.The lymph nodes subsequently underwent pathological examination to determine the presence of metastasis,and the SWE results and pathological assessments were compared.RESULTS A total of 1077 lymph nodes were evaluated;18 and 15 cases of esophageal and gastric cancer were identified,respectively.The optimal cutoff value for lymph node size was calculated to be 5.1 mm,and the area under the curve value was 0.74(95%confidence interval:0.69-0.84).When limited to a lymph node larger than the cut off value,the SWE sensitivity and specificity for metastasis identification were 0.76 and 0.82,respectively.CONCLUSION SWE was useful in detecting lymph node metastases in the upper gastrointestinal tract.展开更多
Euphorbia helioscopia,a natural plant recognized for its anti-tumor properties,has been extensively investigated in various cancers.However,its therapeutic potential in gastric cancer with positive lymph node metastas...Euphorbia helioscopia,a natural plant recognized for its anti-tumor properties,has been extensively investigated in various cancers.However,its therapeutic potential in gastric cancer with positive lymph node metastasis remains underexplored.This study aimed to elucidate the role of E.helioscopia in treating gastric cancer with lymph node metastasis using an integrative approach that combined network pharmacology,molecular docking,and molecular dynamics simulations.Initially,shared target data between E.helioscopia and gastric cancer with positive lymph node metastasis were identified and systematically analyzed.Subsequently,molecular docking was conducted to validate the interactions between key components and targets.Finally,molecular dynamics simulations were employed,with binding free energy calculations performed using the MM-PBSA algorithm.The findings revealed that the primary bioactive compounds of E.helioscopia in this context included quercetin and luteolin,targeting core molecules such as EGFR and MMP9.Key pathways implicated in its mechanism of action included resistance to EGFR tyrosine kinase inhibitors,among others.Molecular docking demonstrated robust binding affinity between the active compounds and critical targets,with molecular dynamics and binding free energy analyses highlighting a particularly stable interaction between luteolin and MMP9.In conclusion,E.helioscopia exhibited a multi-component,multi-target,and multi-pathway therapeutic profile in treating gastric cancer with positive lymph node metastasis.These findings offered valuable theoretical insights supporting its potential clinical application in oncology.展开更多
BACKGROUND Gastrointestinal dual-contrast ultrasonography(DCUS)is characterized by its high resolution,sensitivity,and specificity.AIM To determine the accuracy of DCUS in predicting lymph node metastasis in middle-ag...BACKGROUND Gastrointestinal dual-contrast ultrasonography(DCUS)is characterized by its high resolution,sensitivity,and specificity.AIM To determine the accuracy of DCUS in predicting lymph node metastasis in middle-aged and elderly patients with gastric cancer(GC).METHODS A total of 100 middle-aged and elderly patients with GC admitted to the Fourth Affiliated Hospital of Soochow University(Dushu Lake Hospital,Suzhou,China)between April 2022 and April 2024 were selected.The baseline data and lymph node metastasis status were collected.DCUS combined with intravenous contrast technology was used to calculate the enhancement time(ET),time to peak(TTP),and slope of the ascending branch wash-in rate(WIR).These indicators were used in assessing lymph node metastasis in patients with GC.RESULTS Among 100 middle-aged and elderly patients with GC,35(35.00%)had lymph node metastases.GC patients with lymph node metastasis had a higher propor-tion of stage II TNM classification and higher WIR values than those without lymph node metastasis.The ET and TTP values were lower in patients with lymph node metastases,and all differences were statistically significant(P<0.05).The area under the curve values for ET,TTP,WIR,and combined diagnosis of GC lymph node metastasis using DCUS were all>0.7.Optimal assessment was achieved when the cutoff values for ET,TTP,and WIR were set at 16.32 seconds,10.67 seconds,and 7.02,res-pectively.CONCLUSION DCUS-mediated assessment of ET,TTP,and WIR can effectively predict and evaluate lymph node metastasis status in patients with GC,with higher sensitivity when used in combination.展开更多
BACKGROUND Lymph node metastasis(LNM)is a key prognostic factor in pancreatic cancer(PC).Accurate preoperative prediction of LNM remains challenging.Radiomics offers a noninvasive method to extract quantitative imagin...BACKGROUND Lymph node metastasis(LNM)is a key prognostic factor in pancreatic cancer(PC).Accurate preoperative prediction of LNM remains challenging.Radiomics offers a noninvasive method to extract quantitative imaging features that may aid in predicting LNM.AIM To investigate the potential value of a computed tomography(CT)-based radiomics model in prediction of LNM in PC.METHODS A retrospective analysis was performed on 168 pathologically confirmed PC patients who underwent contrast-enhanced-CT.Among them,107 cases had no LNM,while 61 cases had confirmed LNM.These patients were randomly divided into a training cohort(n=135)and a validation cohort(n=33).A total of 792 radiomics features were extracted,comprising 396 features from the arterial phase and another 396 from the portal venous phase.The Minimum Redundancy Maximum Relevance and Least Absolute Shrinkage and Selection Operator methods were used for feature selection and Radiomics model construction.The receiver operating characteristic curve was employed to assess the diagnostic potential of the model,and DeLong test was used to compare the area under the curve(AUC)values of the model.RESULTS Six radiomics features from the arterial phase and nine from the portal venous phase were selected.The Radscore model demonstrated strong predictive performance for LNM in both the training and test cohorts,with AUC values ranging from 0.86 to 0.94,sensitivity between 66.7% and 91.7%,specificity from 71.4% to 100.0%,accuracy between 78.8%and 91.1%,PPV ranging from 64.7% to 100.0%,and negative predictive value between 84.0% and 93.8%.No significant differences in AUC values were observed between the arterial and portal venous phases in either the training or test set.CONCLUSION The preoperative CT-based radiomics model exhibited robust predictive capability for identifying LNM in PC.展开更多
BACKGROUND Gastric cancer(GC)is frequently diagnosed at advanced stages,often with lymph node metastasis(LNM),which complicates prognosis.Swollen LNM(SLNM)in GC has been linked to poor outcomes,yet its prognostic valu...BACKGROUND Gastric cancer(GC)is frequently diagnosed at advanced stages,often with lymph node metastasis(LNM),which complicates prognosis.Swollen LNM(SLNM)in GC has been linked to poor outcomes,yet its prognostic value requires validation.AIM To evaluate the prognostic significance of SLNM in GC patients undergoing curative-intent gastrectomy.METHODS A retrospective analysis included 507 GC patients with LNM,categorized by SLNM status into positive(SLNM present)and negative(SLNM absent)groups.Survival outcomes were compared between groups,including propensity score matching and multivariate analysis to assess the role of SLNM as an independent prognostic factor.RESULTS One hundred and thirty-nine(27.4%)patients exhibited SLNM,associated with significantly lower 5-year overall survival(OS)compared to non-SLNM patients(13.6%vs 35.8%,P<0.001).After matching,SLNM-positive patients maintained worse OS rates(13.4%vs 21.2%,P=0.006).Multivariate analysis confirmed SLNM as an independent prognostic factor(hazard ratio=1.318,P=0.031).Additionally,T4 stage,N3 stage,and neoadjuvant chemotherapy independently influenced survival outcomes for SLNM-positive patients.Those who received neoadjuvant chemotherapy demonstrated better prognosis.CONCLUSION SLNM is an independent predictor of poor prognosis in GC.Neoadjuvant chemotherapy followed by D2 gastrectomy and adjuvant chemotherapy may offer survival benefits for patients with SLNM.展开更多
The article by Yuan et al accessed the clinicopathologic and prognostic significance of the patterns of lymph node(LN)metastasis in upper and lower gastric cancer(GC).In this article,we will analyze both the strengths...The article by Yuan et al accessed the clinicopathologic and prognostic significance of the patterns of lymph node(LN)metastasis in upper and lower gastric cancer(GC).In this article,we will analyze both the strengths and limitations of this paper.The study’s methodology seems appropriate and proper statistical analyses were applied to identify significant variables.The authors applied the Cox regression model to identify independent risk factors and Kaplan-Meier survival curves to assess prognosis.The researchers found notable differences in cli-nicopathologic variables between patients with upper and lower GC.Addi-tionally,they identified specific LN stations more prone to metastasis in different Siewert classifications of GC.Despite the study’s detailed analysis,it would have been beneficial to explore whether there were survival differences among upper GC patients based on the Siewert classification.Furthermore,the study should have addressed potential confounding factors that might have influenced the results.A more comprehensive analysis could have been achieved by comparing survival outcomes based on LN metastasis patterns.Overall,this article is relevant and provides valuable insights into the significance of LN metastasis patterns in upper GC patients.展开更多
Most papillary thyroid carcinoma(PTC) patients have a good prognosis. However, lymph node metastasis(LNM), the most common manifestation of disease progression, is frequently associated with a poor prognosis.Neverthel...Most papillary thyroid carcinoma(PTC) patients have a good prognosis. However, lymph node metastasis(LNM), the most common manifestation of disease progression, is frequently associated with a poor prognosis.Nevertheless, few studies have focused on the underlying mechanisms of LNM. In the current study, we aimed to investigate the potential role of exosomal circRNAs that contribute to LNM in PTC. We identified 9 000 differentially expressed exosomal circRNAs in PTC patients with LNM, including 684 upregulated and 2 193 downregulated circRNAs. Functional enrichment analysis revealed that these differentially expressed circRNAs were primarily involved in a variety of molecular and signaling pathways correlated with PTC progression and LNM. Through bioinformatics analysis, we identified 14 circRNA-miRNA-mRNA networks related to LNM-associated signaling pathways in PTC. Moreover, both circTACC2-miR-7-EGFR and circBIRC6-miR-24-3p-BCL2L11 axes were verified for their potential involvement in PTC with LNM. Additionally, we identified four upregulated circRNA-related hub genes and eight hub genes correlated with downregulated circRNAs, some of which were validated as being potentially involved in LNM in PTC. Collectively, our findings provide a novel framework for an in-depth investigation of the function of dysregulated exosomal circRNAs and their potential as biomarkers in PTC patients with LNM.展开更多
Objective To analyze the risk factors for lymph node metastasis(LNM)in patients with stage pT1 lung adenocarcinoma to select a more appropriate surgical option.Methods In this retrospective study,294 patients with pos...Objective To analyze the risk factors for lymph node metastasis(LNM)in patients with stage pT1 lung adenocarcinoma to select a more appropriate surgical option.Methods In this retrospective study,294 patients with postoperative pathologically confirmed stage pT1 invasive lung adenocarcinoma were collected and divided into two groups according to whether they had mediastinal or hilar LNM.Patient tumor imaging,pathological features and gene mutations were analyzed,and risk factors that might predict LNM were derived via univariate and multivariate logistic analyses.LNM-related variables were screened by Boruta and least absolute shrinkage and selection operator regression analysis.Results Among the 294 patients,45(15.3%)had positive mediastinal or hilar lymph nodes.There were no significant differences between the two groups in terms of sex,age,or underlying disease.The difference in the percentage of solidity between the two groups was significant,with the higer percentage group showing a more significant difference.The results of multivariate logistic analysis revealed that a high percentage of solid components and wild-type epidermal growth factor receptor(EGFR)were risk factors for LNM.The nomogram for predicting LNM included the consolidation tumor ratio,tumor size,micropapillary and EGFR,with an area under the curve of 93.4%(95%CI:88.7–99.1)in the derivation cohort and 92.3%(95%CI:84.6–99.9)in the validation cohort.Conclusions A high proportion of solid components and wild-type EGFR were risk factors for pT1 stage lung adenocarcinoma,suggesting that the choice of lung segmentectomy needs to be evaluated and selected more cautiously.展开更多
Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surge...Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surgery.This study aimed to develop and validate a computed tomography(CT)-based radiomics and deep learning(DL)fusion model for predicting non-invasive OLNM.Methods:Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed.We developed clinical,radiomics,and radiomics-clinical models using logistic regression.A DL model was established using a three-dimensional squeeze-and-excitation residual network-34(3D SE-ResNet34)and a fusion model was created by integrating seleted clinical,radiomics features and DL features.Model performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Five predictive models were compared;SHapley Additive exPlanations(SHAP)and Gradient-weighted Class Activation Mapping(Grad-CAM)were employed for visualization and interpretation.Results:Overall,358 patients were included:186 in the training cohort,48 in the internal validation cohort,and 124 in the external testing cohort.The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset,with strong performance in internal and external cohorts(AUCs of 0.903 and 0.907,respectively),outperforming single-modal DL models,clinical models,radiomics models,and radiomicsclinical combined models(DeLong test:P<0.05).DCA confirmed its clinical utility,and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities.Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk.Conclusions:The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma,offering a non-invasive tool to refine staging and guide personalized treatment decisions.These results may aid clinicians in optimizing surgical and radiotherapy strategies.展开更多
BACKGROUND Esophageal cancer(EC)is one of the most common malignancies worldwide,and lymph node(LN)metastasis remains one of the leading causes of EC recurrence.Metabolic disorders critically affect cancer progression...BACKGROUND Esophageal cancer(EC)is one of the most common malignancies worldwide,and lymph node(LN)metastasis remains one of the leading causes of EC recurrence.Metabolic disorders critically affect cancer progression,and lipid levels are closely associated with the occurrence of EC and several other tumor types.This study analyzed pretreatment lipid levels to determine their association with LN metastasis.AIM To dissect the possible mechanisms underlying LN metastasis and clarify the prognostic role of lipid profiles in EC.METHODS Serum lipid levels and clinicopathological information were retrospectively collected from 294 patients,and risk factors for LN metastasis were confirmed using a logistic regression model.Latent factors were explored using information from publicly accessible databases and immunofluorescence and immunohistochemical staining techniques.RESULTS High serum levels of low-density lipoprotein(LDL)cholesterol promote LN metastasis in EC,while high-density lipoprotein cholesterol has the opposite role.Information of a public database revealed that LDL receptors LRP5 and LRP6 are highly expressed in ECs,and LRP6 overexpression positively correlated with the infiltration of B lymphocytes and a poor prognosis.Immunofluorescence and immunohistochemical staining revealed that the expression of LRP6 and infiltrated B lymphocytes in patients with≥1 regional LN metastasis,containing N1-3(N+group)were significantly higher than those in the N0 group.LRP6 was also highly expressed in the B lymphocytes of the N+group.There was no difference in CXCL13 expression between the N+and N0 groups.However,CXCR5 expression was significantly higher in the N0 group than in the N+group.CONCLUSION High serum LDL levels can promote LN metastasis in EC,and the mechanisms may be related to LRP6 expression and the infiltration of B lymphocytes.展开更多
Lymph node metastasis(LNM)is a crucial risk factor influencing an unfavorable prognosis in specific cancers.Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targ...Lymph node metastasis(LNM)is a crucial risk factor influencing an unfavorable prognosis in specific cancers.Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets.Nevertheless,the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments.Preclinical models,in this context,serve as the conduit connecting fundamental theories to clinical outcomes.In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms.Using various experimental animals,including mice,diverse methods,such as carcinogen-induced tumorigenesis,tumor cell line or human tumor transplantation,genetic engineering,and humanization,have been used effectively to construct numerous models for tumor LNM.Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis.Transplantation models,using human tumor cell lines or patient-derived tumors,offer a research platform closely mirroring the histology and clinical behavior of human tumors.Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment.Humanized models are used to overcome barriers between human and murine immune systems.Beyond mouse models,various other animal models have unique advantages and limitations,all contributing to exploring LNM.This review summarizes existing in vitro and animal preclinical models,identifies current bottlenecks in preclinical research,and offers an outlook on forthcoming preclinical models.展开更多
Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can p...Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis.An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect.Materials and Methods:We used sequencing analysis of collected serum to screen out exo-miRNA related to LNM in GC.ELISA,qRT-PCR,Western Blot,RNA pull-down assay,Transwell assay,animal experiments,and other experiments were used to verify the results.Results:In this study,we screened out miR-224-3p related to GC progression and LNM in a vascular endothelial growth Factor C(VEGFC)-independent manner.We found that exo-miR-224-3p derived from GC cells could enter human lymphatic endothelial cells(HLECs)and promote the tube formation and migration of HLECs.In addition,it was revealed that miR-224-3p could bind to the 3′UTR region of GSK3B mRNA.Then,we proved that inhibiting the expression of GSK3B could suppress the phosphorylation ofβ-catenin and promote the transcription of PROX1,thus leading to tumor lymphangiogenesis.Furthermore,it was also found that hnRNPA1 mediated the sorting of miR-224-3p into exosomes,and the high expression of PKM2 promoted the secretion of exomiR-224-3p.Conclusions:Our discovery of the exo-miR-224-3p/GSK3B/β-catenin/PROX1 axis may provide a new direction for the clinical treatment of GC.展开更多
Objective: Axillary lymph node dissection(ALND) may be unnecessary in 20%–60% of breast cancer patients with sentinel lymph node(NSLN) metastasis. The aim of the present study was to review the medical records of Chi...Objective: Axillary lymph node dissection(ALND) may be unnecessary in 20%–60% of breast cancer patients with sentinel lymph node(NSLN) metastasis. The aim of the present study was to review the medical records of Chinese patients with early-stage breast cancer and positive NSLN metastasis to identify clinicopathological characteristics as risk factors for non-NSLN metastasis.Methods: The medical records of 2008 early-stage breast cancer patients who received intraoperative sentinel lymph node biopsy(SLNB) between 2006 and 2016 were retrospectively reviewed. These patients were clinically and radiologically lymph nodenegative and had no prior history of receiving neoadjuvant chemotherapy or endocrinotherapy. The clinicopathological characteristics of patients with positive NSLN metastasis who underwent ALND were investigated.Results: In the present study, 296 patients with positive NSLN metastases underwent ALND. Positive non-NSLN metastases were confirmed in 95 patients(32.1%). On univariate analysis, ≥ 3 positive NSLN metastases(P <0.01), NSLN macrometastases(P =0.023), and lymphovascular invasion(P = 0.04) were associated with non-NSLN metastasis(P <0.05). In multivariate analysis, the number of positive SLNs was the most significant predictor of non-SLN metastasis. For patients with 0, 1, 2, or 3 associated risk factors, the non-SLN metastatic rates were 11.5%, 22.5%, 35.2%, and 73.1%, respectively.Conclusions: The number of positive NSLNs, NSLN macrometastases, and lymphovascular invasion were correlated with nonSLN metastasis. The number of positive SLNs was an independent predictor for non-NSLN metastasis. When 2 or 3 risk factors were present in one patient, the probability of non-NSLN was higher than that in the American College of Surgeons Oncology Group Z0011 trial(27.3%); thus, avoiding ALND should be considered carefully.展开更多
Objective: To study the expression of vascular endothelial growth factor C (VEGF-C) in gastric carcinoma and its relationship with lymph node metastasis. Methods: The expression of VEGF-C mRNA in 5 gastric carcinoma c...Objective: To study the expression of vascular endothelial growth factor C (VEGF-C) in gastric carcinoma and its relationship with lymph node metastasis. Methods: The expression of VEGF-C mRNA in 5 gastric carcinoma cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR). Simultaneously, the expression of VEGF-C protein in gastric carcinoma tissues, which were obtained from 63 patients who underwent radical gastrectomy, was detected by immunohistochemistry. Results: Three of the 5 gastric carcinoma cell lines, MKN-45, SGC-7901 and AGS, expressed VEGF-C mRNA. VEGF-C protein was expressed in 52.4% (33/63) of patients. VEGF-C protein expression was more frequently found in tumors with lymph node metastasis than in those without (P<0.01). VEGF-C protein expression was also closely related to lymphatic invasion (P<0.01) and TNM stage (P<0.01). However, there was no significant correlation between VEGF-C expression and the age, gender, tumor size, tumor location, Lauren classification, depth of invasion, and vascular invasion. Conclusion: The expression of VEGF-C is closely related to lymph node metastasis of gastric carcinoma, and lymphangiogenesis might be a new target for treatment of gastric carcinoma.展开更多
AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in...AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.展开更多
Spread into regional lymph node is the major route of metastasis in cervical cancer. Although lymph node status is not involved in the International Federation of Gynecology and Obstetrics staging system of uterine ce...Spread into regional lymph node is the major route of metastasis in cervical cancer. Although lymph node status is not involved in the International Federation of Gynecology and Obstetrics staging system of uterine cervical cancer, the presence or absence of lymph node metastasis provides important information for prognosis and treatment. In this review, we have attempted to focus on the incidence and patterns of lymph node metastasis, and the issues surrounding surgical assessment of lymph nodes. In addition, the preoperative prediction of lymph node status, as well as the intraoperative assessment by sentinel nodes will be reviewed. Finally, lymph node micrometastasis also will be discussed.展开更多
AIM： To investigate whether serum vascular endothelial growth factor-C （SVEGF-C）, VEGF-C, and lymphatic vessel density （LVD） in tumor tissues are related to lymph node metastasis （LNM） and prognosis in gastric ...AIM： To investigate whether serum vascular endothelial growth factor-C （SVEGF-C）, VEGF-C, and lymphatic vessel density （LVD） in tumor tissues are related to lymph node metastasis （LNM） and prognosis in gastric cancer. METHODS： SVEGF-C levels of 80 gastric cancer patients and 20 healthy donors were examined using ELISA. VEGF-C expression and LVD were examined using immunohistochemical staining. Kaplan-Meier survival analysis was performed to determine their influence on the prognosis of the patients. RESULTS： The SVEGF-C level in gastric cancer patients （595.9 ± 201.0 ng/L） was significantly higher （P = 0.000） than controls （360.0 ± 97.4 ng/L）. Both SVEGF-C and LVD were significantly higher in poorly differentiated adenocarcinomas, T3 and T4, LNM, distant metastasis, and pTNM groups Ⅲ and Ⅳ （P = 0.000）. The sensitivity and specificity of SVEGF-C for predicting LNM were 82.8% and 81.8%, respectively （cut-off = 542.5 ng/L）. The positive expression rate of VEGF-C was significantly higher in cancerous than in normal tissues （65% vs 20%; P = 0.001）. VEGF-C expression up-regulation was significantly related to differentiation, depth of invasion, LNM, distant metastasis, and pTNM stage （P = 0.000）. LVD was 10.7 ± 3.1/200 HP in the experimental group vs 4.9 ± 1.3/200 HP in controls （P = 0.000）; LVD in cancerous tissues with and without LNM was 12.0 ± 2.7/200 HP vs 7.6 ± 0.5/200 HP, respectively （P = 0.000）. SVEGF-C and LVD were significantly higher in VEGF-C positive than in negative patients （P = 0.000）; SVEGF-C level was related to LVD （P = 0.000）. Kaplan-Meier survival analysis factors predicating poor prognosis were： SVEGF-C level （P = 0.001）, VEGF-C expression and LVD （both P = 0.000）. CONCLUSION： SVEGF-C level, VEGF-C and LVD are related to LNI and poor prognosis of patients with gastric cancer, SVEGF-C may be a biomarker for LNI in gastric cancer,展开更多
文摘BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.AIM To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.METHODS A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study.The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer’s recommendations along with the normal gingival epithelium as a positive control.All the observations were recorded and Pearson’sχ²test with Fisher exact test was used for statistical analysis.RESULTS Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size.The majority of the patients were in advanced TNM stages(III and IV),and showed intense expression of MMP-9 and MMP-13.CONCLUSION The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness.Intense expression of MMP-9 and MMP-13,irrespective of histological grade of OSCC,correlates well with TNM stage.Consequently,it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors.The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques,hence enhancing the prognosis of patients diagnosed with OSCC.
文摘Gastric cancer(GC)remains a leading cause of cancer mortality.While the extent of nodal involvement is a well-known prognostic factor,the specific entity of swollen lymph node metastasis(SLNM),bulky nodal tumor deposits detectable radiologically or pathologically,has received little attention in staging.Recent data from a study by Cui et al demonstrated that SLNM is an independent predictor of very poor survival in GC.Through robust data and rigorous propensitymatched analyses,SLNM emerged not merely as an anatomical finding but as an independent predictor of poor prognosis,even among patients undergoing curative resection.As precision oncology advances,the findings by Cui et al urge a fundamental rethinking of how SLNM is incorporated into clinical decisionmaking for GC management.In this editorial,we critically examine the prognostic significance of SLNM,challenge its omission from traditional staging frameworks,and advocate for its formal integration into preoperative risk stratification and treatment planning.Recognizing SLNM at diagnosis could unlock intensified neoadjuvant therapy strategies and optimize outcomes for a historically high-risk patient subgroup.
文摘Accurate preoperative prediction of lymph node metastasis is crucial for developing clinical management strategies for patients with esophageal cancer.In this letter,we present our insights and opinions on a new nomogram proposed by Xu et al.Although this research has great potential,there are still concerns re-garding the small sample size,limited consideration of biological complexity,subjective image segmentation,incomplete image feature extraction and statistical analyses.Furthermore,we discuss how to achieve more robust and accurate predictive performance in future research.
基金This study was approved by the Ethics Committee of Nippon Medical School Hospital(No.B-2022-582).
文摘BACKGROUND Tissue hardness is closely related to disease pathophysiology.Shear-wave ela-stography(SWE)is a simple and noninvasive ultrasound technique that has been used to evaluate the presence of lymph node metastases and differentiate between benign and malignant tumors.AIM To investigate SWE usefulness in measuring lymph node hardness to predict metastasis presence or absence in surgically removed lymph nodes.METHODS This observational study obtained data from patients who underwent surgery for esophageal or gastric cancer at Nippon Medical School Hospital.The hardness of the surgically removed lymph nodes was measured using SWE.The lymph nodes with hardness values≥2.2 m/s were considered clinically positive for metastasis,whereas those with lower hardness values were considered clinically negative.The lymph nodes subsequently underwent pathological examination to determine the presence of metastasis,and the SWE results and pathological assessments were compared.RESULTS A total of 1077 lymph nodes were evaluated;18 and 15 cases of esophageal and gastric cancer were identified,respectively.The optimal cutoff value for lymph node size was calculated to be 5.1 mm,and the area under the curve value was 0.74(95%confidence interval:0.69-0.84).When limited to a lymph node larger than the cut off value,the SWE sensitivity and specificity for metastasis identification were 0.76 and 0.82,respectively.CONCLUSION SWE was useful in detecting lymph node metastases in the upper gastrointestinal tract.
基金The Gansu Province University Industrial Support Plan(Grant No.2023CYZC-05)the Cuiying Technology Innovation Project of Lanzhou University Second Hospital(Grant No.CY2022-MS-B04)+1 种基金the Doctoral Students Training Research Fund of Lanzhou University Second Hospital(Grant No.YJS-BD-32)the Gansu Province Drug Regulatory Science Research Project in 2024(Grant No.2024GSMPA032).
文摘Euphorbia helioscopia,a natural plant recognized for its anti-tumor properties,has been extensively investigated in various cancers.However,its therapeutic potential in gastric cancer with positive lymph node metastasis remains underexplored.This study aimed to elucidate the role of E.helioscopia in treating gastric cancer with lymph node metastasis using an integrative approach that combined network pharmacology,molecular docking,and molecular dynamics simulations.Initially,shared target data between E.helioscopia and gastric cancer with positive lymph node metastasis were identified and systematically analyzed.Subsequently,molecular docking was conducted to validate the interactions between key components and targets.Finally,molecular dynamics simulations were employed,with binding free energy calculations performed using the MM-PBSA algorithm.The findings revealed that the primary bioactive compounds of E.helioscopia in this context included quercetin and luteolin,targeting core molecules such as EGFR and MMP9.Key pathways implicated in its mechanism of action included resistance to EGFR tyrosine kinase inhibitors,among others.Molecular docking demonstrated robust binding affinity between the active compounds and critical targets,with molecular dynamics and binding free energy analyses highlighting a particularly stable interaction between luteolin and MMP9.In conclusion,E.helioscopia exhibited a multi-component,multi-target,and multi-pathway therapeutic profile in treating gastric cancer with positive lymph node metastasis.These findings offered valuable theoretical insights supporting its potential clinical application in oncology.
文摘BACKGROUND Gastrointestinal dual-contrast ultrasonography(DCUS)is characterized by its high resolution,sensitivity,and specificity.AIM To determine the accuracy of DCUS in predicting lymph node metastasis in middle-aged and elderly patients with gastric cancer(GC).METHODS A total of 100 middle-aged and elderly patients with GC admitted to the Fourth Affiliated Hospital of Soochow University(Dushu Lake Hospital,Suzhou,China)between April 2022 and April 2024 were selected.The baseline data and lymph node metastasis status were collected.DCUS combined with intravenous contrast technology was used to calculate the enhancement time(ET),time to peak(TTP),and slope of the ascending branch wash-in rate(WIR).These indicators were used in assessing lymph node metastasis in patients with GC.RESULTS Among 100 middle-aged and elderly patients with GC,35(35.00%)had lymph node metastases.GC patients with lymph node metastasis had a higher propor-tion of stage II TNM classification and higher WIR values than those without lymph node metastasis.The ET and TTP values were lower in patients with lymph node metastases,and all differences were statistically significant(P<0.05).The area under the curve values for ET,TTP,WIR,and combined diagnosis of GC lymph node metastasis using DCUS were all>0.7.Optimal assessment was achieved when the cutoff values for ET,TTP,and WIR were set at 16.32 seconds,10.67 seconds,and 7.02,res-pectively.CONCLUSION DCUS-mediated assessment of ET,TTP,and WIR can effectively predict and evaluate lymph node metastasis status in patients with GC,with higher sensitivity when used in combination.
基金Supported by National Natural Science foundation of China,No.82202135,No.82371919,No.82372017,and No.82171925China Postdoctoral Science Foundation,No.2023M741808+4 种基金Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine,No.2024-QNRC2-B16Jiangsu Provincial Key Research and Development Program,No.BE2023789Young Elite Scientists Sponsorship Program by Jiangsu Association for Science and Technology,No.JSTJ-2023-WJ027Project funded by Nanjing Postdoctoral Science Foundation,Natural Science Foundation of Nanjing University of Chinese Medicine,No.XZR2023036Foundation of Excellent Young Doctor of Jiangsu Province Hospital of Chinese Medicine,No.2023QB0112.
文摘BACKGROUND Lymph node metastasis(LNM)is a key prognostic factor in pancreatic cancer(PC).Accurate preoperative prediction of LNM remains challenging.Radiomics offers a noninvasive method to extract quantitative imaging features that may aid in predicting LNM.AIM To investigate the potential value of a computed tomography(CT)-based radiomics model in prediction of LNM in PC.METHODS A retrospective analysis was performed on 168 pathologically confirmed PC patients who underwent contrast-enhanced-CT.Among them,107 cases had no LNM,while 61 cases had confirmed LNM.These patients were randomly divided into a training cohort(n=135)and a validation cohort(n=33).A total of 792 radiomics features were extracted,comprising 396 features from the arterial phase and another 396 from the portal venous phase.The Minimum Redundancy Maximum Relevance and Least Absolute Shrinkage and Selection Operator methods were used for feature selection and Radiomics model construction.The receiver operating characteristic curve was employed to assess the diagnostic potential of the model,and DeLong test was used to compare the area under the curve(AUC)values of the model.RESULTS Six radiomics features from the arterial phase and nine from the portal venous phase were selected.The Radscore model demonstrated strong predictive performance for LNM in both the training and test cohorts,with AUC values ranging from 0.86 to 0.94,sensitivity between 66.7% and 91.7%,specificity from 71.4% to 100.0%,accuracy between 78.8%and 91.1%,PPV ranging from 64.7% to 100.0%,and negative predictive value between 84.0% and 93.8%.No significant differences in AUC values were observed between the arterial and portal venous phases in either the training or test set.CONCLUSION The preoperative CT-based radiomics model exhibited robust predictive capability for identifying LNM in PC.
基金Supported by The Shandong Provincial Medical and Health Science and Technology Youth Project,China,No.202304081355The Weifang Youth Medical Talent Lift Project,Chinaand The Science and Technology Development Project of Affiliated Hospital of Shandong Second Medical University,China,No.2023FYQ004.
文摘BACKGROUND Gastric cancer(GC)is frequently diagnosed at advanced stages,often with lymph node metastasis(LNM),which complicates prognosis.Swollen LNM(SLNM)in GC has been linked to poor outcomes,yet its prognostic value requires validation.AIM To evaluate the prognostic significance of SLNM in GC patients undergoing curative-intent gastrectomy.METHODS A retrospective analysis included 507 GC patients with LNM,categorized by SLNM status into positive(SLNM present)and negative(SLNM absent)groups.Survival outcomes were compared between groups,including propensity score matching and multivariate analysis to assess the role of SLNM as an independent prognostic factor.RESULTS One hundred and thirty-nine(27.4%)patients exhibited SLNM,associated with significantly lower 5-year overall survival(OS)compared to non-SLNM patients(13.6%vs 35.8%,P<0.001).After matching,SLNM-positive patients maintained worse OS rates(13.4%vs 21.2%,P=0.006).Multivariate analysis confirmed SLNM as an independent prognostic factor(hazard ratio=1.318,P=0.031).Additionally,T4 stage,N3 stage,and neoadjuvant chemotherapy independently influenced survival outcomes for SLNM-positive patients.Those who received neoadjuvant chemotherapy demonstrated better prognosis.CONCLUSION SLNM is an independent predictor of poor prognosis in GC.Neoadjuvant chemotherapy followed by D2 gastrectomy and adjuvant chemotherapy may offer survival benefits for patients with SLNM.
文摘The article by Yuan et al accessed the clinicopathologic and prognostic significance of the patterns of lymph node(LN)metastasis in upper and lower gastric cancer(GC).In this article,we will analyze both the strengths and limitations of this paper.The study’s methodology seems appropriate and proper statistical analyses were applied to identify significant variables.The authors applied the Cox regression model to identify independent risk factors and Kaplan-Meier survival curves to assess prognosis.The researchers found notable differences in cli-nicopathologic variables between patients with upper and lower GC.Addi-tionally,they identified specific LN stations more prone to metastasis in different Siewert classifications of GC.Despite the study’s detailed analysis,it would have been beneficial to explore whether there were survival differences among upper GC patients based on the Siewert classification.Furthermore,the study should have addressed potential confounding factors that might have influenced the results.A more comprehensive analysis could have been achieved by comparing survival outcomes based on LN metastasis patterns.Overall,this article is relevant and provides valuable insights into the significance of LN metastasis patterns in upper GC patients.
基金National Natural Science Foundation of China (Grant No. 81800698)Jiangsu Provincial Medical Key Discipline Cultivation Unit (Grant No. JSDW202241)+1 种基金Research Project of Jiangsu Commission of Health (Grant No. H2023053)Zhenjiang Science and the Technology Planning Project (Grant Nos. SH2023006and SH2023008)。
文摘Most papillary thyroid carcinoma(PTC) patients have a good prognosis. However, lymph node metastasis(LNM), the most common manifestation of disease progression, is frequently associated with a poor prognosis.Nevertheless, few studies have focused on the underlying mechanisms of LNM. In the current study, we aimed to investigate the potential role of exosomal circRNAs that contribute to LNM in PTC. We identified 9 000 differentially expressed exosomal circRNAs in PTC patients with LNM, including 684 upregulated and 2 193 downregulated circRNAs. Functional enrichment analysis revealed that these differentially expressed circRNAs were primarily involved in a variety of molecular and signaling pathways correlated with PTC progression and LNM. Through bioinformatics analysis, we identified 14 circRNA-miRNA-mRNA networks related to LNM-associated signaling pathways in PTC. Moreover, both circTACC2-miR-7-EGFR and circBIRC6-miR-24-3p-BCL2L11 axes were verified for their potential involvement in PTC with LNM. Additionally, we identified four upregulated circRNA-related hub genes and eight hub genes correlated with downregulated circRNAs, some of which were validated as being potentially involved in LNM in PTC. Collectively, our findings provide a novel framework for an in-depth investigation of the function of dysregulated exosomal circRNAs and their potential as biomarkers in PTC patients with LNM.
文摘Objective To analyze the risk factors for lymph node metastasis(LNM)in patients with stage pT1 lung adenocarcinoma to select a more appropriate surgical option.Methods In this retrospective study,294 patients with postoperative pathologically confirmed stage pT1 invasive lung adenocarcinoma were collected and divided into two groups according to whether they had mediastinal or hilar LNM.Patient tumor imaging,pathological features and gene mutations were analyzed,and risk factors that might predict LNM were derived via univariate and multivariate logistic analyses.LNM-related variables were screened by Boruta and least absolute shrinkage and selection operator regression analysis.Results Among the 294 patients,45(15.3%)had positive mediastinal or hilar lymph nodes.There were no significant differences between the two groups in terms of sex,age,or underlying disease.The difference in the percentage of solidity between the two groups was significant,with the higer percentage group showing a more significant difference.The results of multivariate logistic analysis revealed that a high percentage of solid components and wild-type epidermal growth factor receptor(EGFR)were risk factors for LNM.The nomogram for predicting LNM included the consolidation tumor ratio,tumor size,micropapillary and EGFR,with an area under the curve of 93.4%(95%CI:88.7–99.1)in the derivation cohort and 92.3%(95%CI:84.6–99.9)in the validation cohort.Conclusions A high proportion of solid components and wild-type EGFR were risk factors for pT1 stage lung adenocarcinoma,suggesting that the choice of lung segmentectomy needs to be evaluated and selected more cautiously.
基金supported by the National Natural Science Foundation of China(No.82272845)the Natural Science Foundation of Shandong(No.ZR2023ZD26).
文摘Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surgery.This study aimed to develop and validate a computed tomography(CT)-based radiomics and deep learning(DL)fusion model for predicting non-invasive OLNM.Methods:Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed.We developed clinical,radiomics,and radiomics-clinical models using logistic regression.A DL model was established using a three-dimensional squeeze-and-excitation residual network-34(3D SE-ResNet34)and a fusion model was created by integrating seleted clinical,radiomics features and DL features.Model performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Five predictive models were compared;SHapley Additive exPlanations(SHAP)and Gradient-weighted Class Activation Mapping(Grad-CAM)were employed for visualization and interpretation.Results:Overall,358 patients were included:186 in the training cohort,48 in the internal validation cohort,and 124 in the external testing cohort.The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset,with strong performance in internal and external cohorts(AUCs of 0.903 and 0.907,respectively),outperforming single-modal DL models,clinical models,radiomics models,and radiomicsclinical combined models(DeLong test:P<0.05).DCA confirmed its clinical utility,and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities.Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk.Conclusions:The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma,offering a non-invasive tool to refine staging and guide personalized treatment decisions.These results may aid clinicians in optimizing surgical and radiotherapy strategies.
文摘BACKGROUND Esophageal cancer(EC)is one of the most common malignancies worldwide,and lymph node(LN)metastasis remains one of the leading causes of EC recurrence.Metabolic disorders critically affect cancer progression,and lipid levels are closely associated with the occurrence of EC and several other tumor types.This study analyzed pretreatment lipid levels to determine their association with LN metastasis.AIM To dissect the possible mechanisms underlying LN metastasis and clarify the prognostic role of lipid profiles in EC.METHODS Serum lipid levels and clinicopathological information were retrospectively collected from 294 patients,and risk factors for LN metastasis were confirmed using a logistic regression model.Latent factors were explored using information from publicly accessible databases and immunofluorescence and immunohistochemical staining techniques.RESULTS High serum levels of low-density lipoprotein(LDL)cholesterol promote LN metastasis in EC,while high-density lipoprotein cholesterol has the opposite role.Information of a public database revealed that LDL receptors LRP5 and LRP6 are highly expressed in ECs,and LRP6 overexpression positively correlated with the infiltration of B lymphocytes and a poor prognosis.Immunofluorescence and immunohistochemical staining revealed that the expression of LRP6 and infiltrated B lymphocytes in patients with≥1 regional LN metastasis,containing N1-3(N+group)were significantly higher than those in the N0 group.LRP6 was also highly expressed in the B lymphocytes of the N+group.There was no difference in CXCL13 expression between the N+and N0 groups.However,CXCR5 expression was significantly higher in the N0 group than in the N+group.CONCLUSION High serum LDL levels can promote LN metastasis in EC,and the mechanisms may be related to LRP6 expression and the infiltration of B lymphocytes.
基金supported by the Fundamental Research Funds for the Central Universities(Wuhan University,Clinical Medicine+X,No.2042024YXB017)the Hubei Province Chinese Medicine Research Project(No.ZY2023Q015)+2 种基金the National Natural Science Foundation of China(No.61904057)the Natural Science Foundation of Hubei Province(No.2023AFB665)the Medical Young Talents Program of Hubei Province,Wuhan Young Medical Talents Training Project,China.
文摘Lymph node metastasis(LNM)is a crucial risk factor influencing an unfavorable prognosis in specific cancers.Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets.Nevertheless,the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments.Preclinical models,in this context,serve as the conduit connecting fundamental theories to clinical outcomes.In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms.Using various experimental animals,including mice,diverse methods,such as carcinogen-induced tumorigenesis,tumor cell line or human tumor transplantation,genetic engineering,and humanization,have been used effectively to construct numerous models for tumor LNM.Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis.Transplantation models,using human tumor cell lines or patient-derived tumors,offer a research platform closely mirroring the histology and clinical behavior of human tumors.Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment.Humanized models are used to overcome barriers between human and murine immune systems.Beyond mouse models,various other animal models have unique advantages and limitations,all contributing to exploring LNM.This review summarizes existing in vitro and animal preclinical models,identifies current bottlenecks in preclinical research,and offers an outlook on forthcoming preclinical models.
基金supported by grants from the National Natural Science Foundation of China(Nos.82072664,81974374,82173125,82103677).
文摘Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis.An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect.Materials and Methods:We used sequencing analysis of collected serum to screen out exo-miRNA related to LNM in GC.ELISA,qRT-PCR,Western Blot,RNA pull-down assay,Transwell assay,animal experiments,and other experiments were used to verify the results.Results:In this study,we screened out miR-224-3p related to GC progression and LNM in a vascular endothelial growth Factor C(VEGFC)-independent manner.We found that exo-miR-224-3p derived from GC cells could enter human lymphatic endothelial cells(HLECs)and promote the tube formation and migration of HLECs.In addition,it was revealed that miR-224-3p could bind to the 3′UTR region of GSK3B mRNA.Then,we proved that inhibiting the expression of GSK3B could suppress the phosphorylation ofβ-catenin and promote the transcription of PROX1,thus leading to tumor lymphangiogenesis.Furthermore,it was also found that hnRNPA1 mediated the sorting of miR-224-3p into exosomes,and the high expression of PKM2 promoted the secretion of exomiR-224-3p.Conclusions:Our discovery of the exo-miR-224-3p/GSK3B/β-catenin/PROX1 axis may provide a new direction for the clinical treatment of GC.
文摘Objective: Axillary lymph node dissection(ALND) may be unnecessary in 20%–60% of breast cancer patients with sentinel lymph node(NSLN) metastasis. The aim of the present study was to review the medical records of Chinese patients with early-stage breast cancer and positive NSLN metastasis to identify clinicopathological characteristics as risk factors for non-NSLN metastasis.Methods: The medical records of 2008 early-stage breast cancer patients who received intraoperative sentinel lymph node biopsy(SLNB) between 2006 and 2016 were retrospectively reviewed. These patients were clinically and radiologically lymph nodenegative and had no prior history of receiving neoadjuvant chemotherapy or endocrinotherapy. The clinicopathological characteristics of patients with positive NSLN metastasis who underwent ALND were investigated.Results: In the present study, 296 patients with positive NSLN metastases underwent ALND. Positive non-NSLN metastases were confirmed in 95 patients(32.1%). On univariate analysis, ≥ 3 positive NSLN metastases(P <0.01), NSLN macrometastases(P =0.023), and lymphovascular invasion(P = 0.04) were associated with non-NSLN metastasis(P <0.05). In multivariate analysis, the number of positive SLNs was the most significant predictor of non-SLN metastasis. For patients with 0, 1, 2, or 3 associated risk factors, the non-SLN metastatic rates were 11.5%, 22.5%, 35.2%, and 73.1%, respectively.Conclusions: The number of positive NSLNs, NSLN macrometastases, and lymphovascular invasion were correlated with nonSLN metastasis. The number of positive SLNs was an independent predictor for non-NSLN metastasis. When 2 or 3 risk factors were present in one patient, the probability of non-NSLN was higher than that in the American College of Surgeons Oncology Group Z0011 trial(27.3%); thus, avoiding ALND should be considered carefully.
文摘Objective: To study the expression of vascular endothelial growth factor C (VEGF-C) in gastric carcinoma and its relationship with lymph node metastasis. Methods: The expression of VEGF-C mRNA in 5 gastric carcinoma cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR). Simultaneously, the expression of VEGF-C protein in gastric carcinoma tissues, which were obtained from 63 patients who underwent radical gastrectomy, was detected by immunohistochemistry. Results: Three of the 5 gastric carcinoma cell lines, MKN-45, SGC-7901 and AGS, expressed VEGF-C mRNA. VEGF-C protein was expressed in 52.4% (33/63) of patients. VEGF-C protein expression was more frequently found in tumors with lymph node metastasis than in those without (P<0.01). VEGF-C protein expression was also closely related to lymphatic invasion (P<0.01) and TNM stage (P<0.01). However, there was no significant correlation between VEGF-C expression and the age, gender, tumor size, tumor location, Lauren classification, depth of invasion, and vascular invasion. Conclusion: The expression of VEGF-C is closely related to lymph node metastasis of gastric carcinoma, and lymphangiogenesis might be a new target for treatment of gastric carcinoma.
基金Supported by The National Natural Science Foundation of China, No. 30772542
文摘AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.
基金This work is supported by the Natural Science Foundation of Hubei Provice （No. 2015CKB739）.
文摘Spread into regional lymph node is the major route of metastasis in cervical cancer. Although lymph node status is not involved in the International Federation of Gynecology and Obstetrics staging system of uterine cervical cancer, the presence or absence of lymph node metastasis provides important information for prognosis and treatment. In this review, we have attempted to focus on the incidence and patterns of lymph node metastasis, and the issues surrounding surgical assessment of lymph nodes. In addition, the preoperative prediction of lymph node status, as well as the intraoperative assessment by sentinel nodes will be reviewed. Finally, lymph node micrometastasis also will be discussed.
文摘AIM： To investigate whether serum vascular endothelial growth factor-C （SVEGF-C）, VEGF-C, and lymphatic vessel density （LVD） in tumor tissues are related to lymph node metastasis （LNM） and prognosis in gastric cancer. METHODS： SVEGF-C levels of 80 gastric cancer patients and 20 healthy donors were examined using ELISA. VEGF-C expression and LVD were examined using immunohistochemical staining. Kaplan-Meier survival analysis was performed to determine their influence on the prognosis of the patients. RESULTS： The SVEGF-C level in gastric cancer patients （595.9 ± 201.0 ng/L） was significantly higher （P = 0.000） than controls （360.0 ± 97.4 ng/L）. Both SVEGF-C and LVD were significantly higher in poorly differentiated adenocarcinomas, T3 and T4, LNM, distant metastasis, and pTNM groups Ⅲ and Ⅳ （P = 0.000）. The sensitivity and specificity of SVEGF-C for predicting LNM were 82.8% and 81.8%, respectively （cut-off = 542.5 ng/L）. The positive expression rate of VEGF-C was significantly higher in cancerous than in normal tissues （65% vs 20%; P = 0.001）. VEGF-C expression up-regulation was significantly related to differentiation, depth of invasion, LNM, distant metastasis, and pTNM stage （P = 0.000）. LVD was 10.7 ± 3.1/200 HP in the experimental group vs 4.9 ± 1.3/200 HP in controls （P = 0.000）; LVD in cancerous tissues with and without LNM was 12.0 ± 2.7/200 HP vs 7.6 ± 0.5/200 HP, respectively （P = 0.000）. SVEGF-C and LVD were significantly higher in VEGF-C positive than in negative patients （P = 0.000）; SVEGF-C level was related to LVD （P = 0.000）. Kaplan-Meier survival analysis factors predicating poor prognosis were： SVEGF-C level （P = 0.001）, VEGF-C expression and LVD （both P = 0.000）. CONCLUSION： SVEGF-C level, VEGF-C and LVD are related to LNI and poor prognosis of patients with gastric cancer, SVEGF-C may be a biomarker for LNI in gastric cancer,
