Molecular profiling of biliary tract cancers(BTCs)has paved the way for a broader range of therapeutic options,leading to improved survival outcomes.Given the challenges of tissue evaluation in BTCs,circulating tumor ...Molecular profiling of biliary tract cancers(BTCs)has paved the way for a broader range of therapeutic options,leading to improved survival outcomes.Given the challenges of tissue evaluation in BTCs,circulating tumor DNA(ct-DNA)has emerged as a promising non-invasive biomarker for genomic profiling.Bile has been proven to be a reliable ctDNA source,demonstrating higher concordance with tumor tissue than plasma.More importantly,ctDNA provides valuable insights into both clonal evolution and treatment response,including the detection of resistance mechanisms and mutation clearance,which are often associated with disease control.Although its role in recurrence monitoring remains investigational,early studies suggest that ctDNA detection may precede radiological recurrences.This review examines recent advancements in ctDNA analysis for patients with BTC,highlighting key developments,current clinical implications,and ongoing challenges.Large-scale prospective studies are needed to validate the clinical utility of ctDNA and to support its integration into BTC management.展开更多
Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks...Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.展开更多
Given the growing burden of colorectal cancer(CRC)as a global health challenge,it becomes imperative to focus on strategies that can mitigate its impact.Posttreatment surveillance has emerged as essential for early de...Given the growing burden of colorectal cancer(CRC)as a global health challenge,it becomes imperative to focus on strategies that can mitigate its impact.Posttreatment surveillance has emerged as essential for early detection of recurrence,significantly improving patient outcomes.However,intensive surveillance strategies have shown mixed results compared to less intensive methods,emphasizing the necessity for personalized,risk-adapted approaches.The observed suboptimal adherence to existing surveillance protocols underscores the urgent need for more tailored and efficient strategies.In this context,circulating tumor DNA(ctDNA)emerges as a promising biomarker with significant potential to revolutionize post-treatment surveillance,demonstrating high specificity[0.95,95%confidence interval(CI):0.91-0.97]and robust diagnostic odds(37.6,95%CI:20.8-68.0)for recurrence detection.Furthermore,artificial intelligence and machine learning models integrating patient-specific and tumor features can enhance risk stratification and optimize surveillance strategies.The reported area under the receiver operating characteristic curve,measuring artificial intelligence model performance in predicting CRC recurrence,ranged from 0.581 and 0.593 at the lowest to 0.979 and 0.978 at the highest in training and validation cohorts,respectively.Despite this promise,addressing cost,accessibility,and extensive validation remains crucial for equitable integration into clinical practice.展开更多
BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitiv...BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.展开更多
Breast cancer remains a leading cause of cancer-related death in women worldwide.Emerging evidence highlights the central roles of breast cancer stem cells(BCSCs)and circulating tumor cells(CTCs)in tumor initiation,pr...Breast cancer remains a leading cause of cancer-related death in women worldwide.Emerging evidence highlights the central roles of breast cancer stem cells(BCSCs)and circulating tumor cells(CTCs)in tumor initiation,progression,therapeutic resistance,and metastasis.BCSCs self-renew and drive intertumoral heterogeneity,while CTCs disseminate from primary tumors into the bloodstream,seeding distant sites.These populations share molecular features,including stemness and epithelial-mesenchymal transition markers,supporting the concept that a subset of CTCs acquires stem-like traits,enhancing metastatic potential and resistance to standard therapies.This review synthesizes current knowledge on BCSC molecular programs,key signaling pathways(e.g.,Wnt,Notch,Hedgehog,Janus kinase/signal transducer and activator of transcription),and microenvironmental interactions that sustain stemness.It also examines mechanisms of CTC intravasation,state-dependent detection strategies,and their diagnostic and prognostic utility.We further highlight the adaptive plasticity of cancer stem celllike CTCs,their contributions to drug resistance,and opportunities to target these phenotypes for personalized treatment.Clarifying the biological links between BCSCs and CTCs could enable earlier detection of hidden metastasis and inform combination therapies aimed at both stemness and dissemination.As multimodal detection improves and functional profiling matures,integrating BCSC/CTC analyses into routine care may refine risk stratification and guide individualized management.展开更多
Circulating tumor DNA(ctDNA)is the free DNA released by tumor or circulating tumor cells,which is associated with many tumor characteristics and can be used as a biomarker for early screening,monitoring,prognosis,and ...Circulating tumor DNA(ctDNA)is the free DNA released by tumor or circulating tumor cells,which is associated with many tumor characteristics and can be used as a biomarker for early screening,monitoring,prognosis,and prediction of therapeutic response in patients with cancer.The field of gastric cancer is very attractive because there are no high-quality screening,monitoring,or prediction methods.Gastric cancer is characterized by great tumor heterogeneity,great differences in genetic and epigenetic characteristics among different subgroups of gastric cancer,and high sensitivity and specificity of methylated ctDNA,which is conducive to the identification of tumor genotypes and the formulation of accurate diagnostic and treatment strategies.In addition,many studies have confirmed that methylated DNA has unique advantages in predicting treatment response,adjuvant therapy,and drug resistance and can be used to increase the efficacy of chemotherapy regimens,improve the chemotherapy response of patients in the future,and even treat multidrug resistance.However,methylated ctDNA also faces many problems,such as low sensitivity and specificity in a single target,limited association between some gastric cancer subtypes and ctDNA,risk of off-target effects,and lack of large-sample and high-quality clinical research evidence.This review mainly summarizes the current research on the DNA methylation of circulating gastric cancer tumors and links these findings with the early screening of gastric cancer,recurrence monitoring,and potential treatment opportunities.With the advancement of technology and the deepening of cross-research between doctors and professionals,ctDNA detection will reveal more disease information and become an important basis for the field of gastric cancer and precision medicine treatment.展开更多
Early diagnosis and accurate boundary delineation are the key steps of tumor precision medicine.Circulating tumor cells(CTCs)detection of liquid biopsy can provide abundant information for early diagnosis of cancer.Hi...Early diagnosis and accurate boundary delineation are the key steps of tumor precision medicine.Circulating tumor cells(CTCs)detection of liquid biopsy can provide abundant information for early diagnosis of cancer.High detection specificity and good enrichment features are two key factors for CTCs accurate identification in peripheral blood sample.For this purpose,iron oxide(IO)-based surface-enhanced Raman scattering(SERS)bioprobes with good biocompatibility,high detection sensitivity,remarkable detection specificity,and good enrichment efficiency,were developed for detecting different types of CTCs.Magnetic SERS bioprobes combined with programmed death ligand-1(PD-L1)antibody are regarded as an effective way to boost the targeting ability and detection specificity,benefiting for accurately capturing and identifying rare CTCs.Four types of CTCs with different PD-L1 expression were accurately distinguished among white blood cells via high-resolution SERS mapping images and stable Raman signals.Subsequently,CTCs blood samples obtained from the triple negative breast cancer patients were also successfully recognized compared to that of health people,indicating IO@AR@PDA-a PD-L1 SERS bioprobe possessed great potential for CTCs detection in liquid biopsy.Additionally,IO-based bioprobe exhibited excellent dual-modal imaging abilities of high-resolution SERS imaging mode and microimaging magnetic resonance imaging mode.These two highly complementary imaging modes endowed IO-based bioprobes unrivalled capacity in tumor boundary differentiation,supporting tumor accurate resection and precise surgery.To our best knowledge,this is the first time that biocompatible IO-based SERS bioprobes without noble metal element were reported not only for CTCs accurate detection,but also for precise tumor boundary delineation,showing great advantages in tumor diagnosis and treatment.展开更多
BACKGROUND Some patients with resectable or borderline resectable pancreatic ductal adenocarcinoma(PDAC)may have distant metastases,undetected on preoperative imaging or early recurrence,within 6 months after surgery....BACKGROUND Some patients with resectable or borderline resectable pancreatic ductal adenocarcinoma(PDAC)may have distant metastases,undetected on preoperative imaging or early recurrence,within 6 months after surgery.Occult metastases(OMs)must be accurately predicted to optimize multidisciplinary treatment.AIM To investigate the efficacy of circulating tumor DNA(ctDNA)in predicting OM.METHODS Two Japanese institutions prospectively collected preoperative plasma samples from PDAC patients between July 2019 and September 2021 and evaluated ctDNA using a targeted next-generation sequencing panel covering 52 cancer-related genes.RESULTS Among 135 PDAC patients,38 had OM and 35 were positive for ctDNA.The ctDNA positivity rate was significantly higher in patients with OM than in patients without OM.ctDNA-positive patients had significantly shorter median recurrence-free survival than ctDNA-negative patients.Logistic multivariate regression revealed ctDNA positivity as an independent predictor of OM.CONCLUSION Preoperative ctDNA in resectable PDAC is an independent predictor of OM and indicates poor prognosis following pancreatectomy and may be a useful biomarker in determining multidisciplinary patient care.展开更多
BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer(GC)patients.To optimize treatment stratification and management,there is an urgent need...BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer(GC)patients.To optimize treatment stratification and management,there is an urgent need for efficient and non-invasive biomarkers.A meta-analysis on the prognostic role of circulating tumor cells(CTCs)in GC revealed a strong association between CTCs and patient prognosis.Among CTC subtypes,Interstitial CTCs(I-CTCs)exhibited the strongest invasiveness.This study innovatively investigated the expression profile of I-CTCs in advanced GC patients to evaluate their clinical utility.AIM To evaluate the clinical utility of I-CTCs as a non-invasive prognostic biomarker in advanced GC.To investigate the correlation between I-CTC count thresholds and chemotherapy efficacy in advanced GC patients.To establish the potential of preoperative I-CTC profiling for optimizing treatment stratification and postoperative surveillance.METHODS This study retrospectively analyzed 59 patients with advanced GC treated at the General Surgery Clinical Medical Center of Gansu Provincial Hospital between October 2019 and October 2020.The expression levels of I-CTCs were measured,and patient survival was monitored.The receiver operating characteristic curve was plotted to determine the optimal cut-off value for I-CTCs expression levels.Based on this cut-off value,59 GC patients were grouped into positive and negative groups.The differences in clinicopathological characteristics between the two groups were analyzed.Patient survival was follow-up and recorded until October 2022.Plotting survival curves and performing univariate and multifactorial analyses of patient prognostic factors.The Kaplan-Meier method and Cox regression model were used,respectively.RESULTS A total of 59 patients were included in this study,and receiver operating characteristic curve analysis showed that the best cut-off value for I-CTCs was 5,with an area under the curve of 0.8356(95%CI:0.7122-0.9590).The I-CTC count of≥5 defines the positive group,while counts<5 are classified as the negative group.Positive I-CTCs correlated with the degree of tumor differentiation and disease progression(P<0.05).16 of 59 patients received neoadjuvant chemotherapy.There were divided into progressive disease and disease control groups based on response to neoadjuvant chemotherapy.Patients in the I-CTCs-negative group had longer overall survival and disease-free survival than those in the positive group(P<0.05).Multifactorial analysis revealed that I-CTCs positivity(HR=13.323,95%CI:1.675-105.962,P=0.014)was an independent risk factor for survival in patients with advanced GC.CONCLUSION In patients with advanced GC,an I-CTC count of≥5 is associated with both poor prognosis and reduced chemotherapy efficacy.I-CTCs may serve as a valuable preoperative biomarker for predicting the prognosis of advanced GC.展开更多
Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is becoming more popular as a diagnostic tool in the clinical management of breast cancer.Elevated concentrations of these biomarkers duri...Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is becoming more popular as a diagnostic tool in the clinical management of breast cancer.Elevated concentrations of these biomarkers during cancer treatment may be used as markers for cancer progression as well as to understand the mechanisms underlying metastasis and treatment resistance.Thus,these circulating markers serve as tools for cancer assessing and monitoring through a simple,non-invasive blood draw.However,despite several study results currently noting a potential clinical impact of ctDNA mutation tracking,the method is not used clinically in cancer diagnosis among patients and more studies are required to confirm it.This review focuses on understanding circulating tumor biomarkers,especially in breast cancer.展开更多
BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always problematic.To use liquid biopsies clinical...BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always problematic.To use liquid biopsies clinically,it will be very important to address these questions.AIM To assess the origin of ctDNA,clarify the dynamics of ctDNA levels,assess ctDNA levels by using a xenograft mouse after treatment,and to determine whether tumor volume and invasion are related to ctDNA levels.METHODS Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell line.Groups of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA analysis.Analysis of ctDNA was performed by droplet digital PCR,using the human telomerase reverse transcriptase(hTERT)gene.RESULTS Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week 8.No hTERT was detected at week 4,but it was detected at week 8.However,in four-site xenograft mice,hTERT was detected both at week 4 and week 6.These experiments revealed that both tumor invasion and tumor volume were asso ciated with the detection of ctDNA.In resection experiments,hTERT was detected at resection,but had decreased by 6 h,and was no longer detected 1 and 3 d after resection.CONCLUSION We clarified the origin and dynamics of ctDNA,showing that tumor volume is an important factor.We also found that when the tumor was completely resected,ctDNA was absent after one or more days.展开更多
Atypical fibroxanthomas (AFX) are rare skin tumors. These generally are superficial tumors, usually <3 cm red, fleshy, ulcerated skin lesions, that characteristically occur on sun-damaged skin, sometimes in immunoc...Atypical fibroxanthomas (AFX) are rare skin tumors. These generally are superficial tumors, usually <3 cm red, fleshy, ulcerated skin lesions, that characteristically occur on sun-damaged skin, sometimes in immunocompromised or previously irradiated patients. These are part of a spectrum of more aggressive fibro-histiocytic neoplasms. In the older literature, these have been termed aggressive or metastatic AFX, but currently these have been reclassified as pleomorphic dermal sarcomas (PDS) and systemic undifferentiated pleomorphic sarcoma (UPS, formerly malignant fibrohistiocytic sarcoma, MFH). We present the case of a 64-year old woman who developed a deeply invasive PDS on the vertex of her scalp invading to the galea, with in-transit scalp metastases. Very little information is available about optimal treatment of metastatic PDS lesions. The patient was initially treated with 2 cycles of epirubicin/ifosfamide chemotherapy, resulting in life-threatening complications. A pretreatment peripheral blood sample was sent for CTC-derived colony assay. This sample grew 8 colonies from 10 ml blood. The tumor failed to respond to epirubicin and ifosfamide, and after several months of hospitalization, a second peripheral blood CTC-derived colony assay grew >376 colonies. The patient could not tolerate additional chemotherapy. She was therefore treated with the oral targeted agent pazopanib. The patient developed a dramatic biopsy-confirmed complete response. After 11 months of pazopanib treatment, a repeat CTC-derived culture sample grew only 8 colonies/10 ml blood. The complete response to pazopanib is still ongoing at over 41 months. To our knowledge, this is the first demonstration of clinical complete response of a PDS tumor following targeted therapy. An additional novel feature was the demonstration that CTC-derived colonies could be grown from the blood of a PDS patient. The number of colonies appeared to correlate with the clinical treatment response and seemed to function as a potential prognostic marker.展开更多
Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biolo...Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biological information of tumor tissue,provide a new perspective and dimension for the study of tumor metastasis,progression,chemotherapy sensitivity and drug resistance.Cerebrospinal fluid(CSF)circulates through the ventricle and spinal cord cistern,which can better maintain the original information of tumor cells compared with the complicated environments of tissues and plasma.Study on the dynamic changes of CTCs in the CSF of the central nervous system(CNS)is relatively rare.However,the analysis of CTCs in CSF can be used to guide the treatment of gliomas and reveal the patho-physiological and genetic mechanisms of tumor cell metastasis to the CSF.This paper reviews the progress in the research on CTC detection in gliomas.展开更多
Hepatocellular carcinoma(HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor...Hepatocellular carcinoma(HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor. Therefore, to provide optimal treatment for each patient with HCC, more precise and effective biomarkers are urgently needed which could facilitate a more detailed individualized decision-making during HCC treatment, including the following; risk assessment, early cancer detection, prediction of treatment or prognostic outcome. In the blood of cancer patients, accumulating evidence about circulating tumor cells and cell-free nucleic acids has suggested their potent clinical utilities as novel biomarker. This concept, so-called "liquid biopsy" is widely known as an alternative approach to cancer tissue biopsy. This method might facilitate a more sensitive diagnosis and better decision-making by obtaining genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. In this article, we review recent developments based on the available literature on both circulating tumor cells and cell-free nucleic acids in cancer patients, especially focusing on Hepatocellular carcinoma.展开更多
AIM: To investigate the feasibility of separation and cultivation of circulating tumor cells (CTCs) in pancreatic cancer (PaC) using a filtration device.
To improve the clinical outcomes of cancer patients, early detection and accurate monitoring of diseases are necessary. Numerous genetic and epigenetic alterations contribute to oncogenesis and cancer progression, and...To improve the clinical outcomes of cancer patients, early detection and accurate monitoring of diseases are necessary. Numerous genetic and epigenetic alterations contribute to oncogenesis and cancer progression, and analyses of these changes have been increasingly utilized for diagnostic, prognostic and therapeutic purposes in malignant diseases including gastric cancer (GC). Surgical and/or biopsy specimens are generally used to understand the tumor-associated alterations; however, those approaches cannot always be performed because of their invasive characteristics and may fail to reflect current tumor dynamics and drug sensitivities, which may change during the therapeutic process. Therefore, the importance of developing a non-invasive biomarker with the ability to monitor real-time tumor dynamics should be emphasized. This concept, so called “liquid biopsy”, would provide an ideal therapeutic strategy for an individual cancer patient and would facilitate the development of “tailor-made” cancer management programs. In the blood of cancer patients, the presence and potent utilities of circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) such as DNA, mRNA and microRNA have been recognized, and their clinical relevance is attracting considerable attention. In this review, we discuss recent developments in this research field as well as the relevance and future perspectives of CTCs and cfNAs in cancer patients, especially focusing on GC.展开更多
AIM To perform a meta-analysis of the related studies to assess whether circulating tumor cells(CTCs) can be used as a prognostic marker of esophageal cancer.METHODS Pub Med, Embase, Cochrane Library and references in...AIM To perform a meta-analysis of the related studies to assess whether circulating tumor cells(CTCs) can be used as a prognostic marker of esophageal cancer.METHODS Pub Med, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival(OS). The meta-analysis was performed using the random effects model, with hazard ratio(HR), risk ratio(RR) and 95% confidence intervals(95%CIs) as effect measures.RESULTS Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression(HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS(HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage(RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage(RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer.CONCLUSION Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted.展开更多
Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed...Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients＇ clinical prognosis.Methods： The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment（SE） and immunostaining-fluorescence in situ hybridization（i FISH）platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.Results： CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 m L and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival（PFS） and overall survival（OS）. In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.Conclusions： Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.展开更多
BACKGROUND One of the most notable applications for circulating tumor DNA(ctDNA)detection in peripheral blood of patients with metastatic colorectal cancer(mCRC)is a long-term postoperative follow-up.Sometimes referre...BACKGROUND One of the most notable applications for circulating tumor DNA(ctDNA)detection in peripheral blood of patients with metastatic colorectal cancer(mCRC)is a long-term postoperative follow-up.Sometimes referred to as a“liquid(re)biopsy”it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals(months or even weeks).The presence of the disease and the actual extent of the tumor burden(tumor mass)within the patient’s body can be monitored.This is of particular importance,especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence.AIM To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer.METHODSA total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers.Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling.In addition to the baseline ctDNA testing prior to surgery,a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals.The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient.RESULTS Among the monitored patients,the R0(curative)resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures(26/28,93%).In the remaining cases of R0 surgeries that displayed ctDNA,both patients were diagnosed with a recurrence of the disease after 6 months.In 7 patients who underwent an R1 resection,4 ctDNA positivities(4/7,57%)were detected after surgery and associated with the confirmation of early disease recurrence(after 3 to 7 months).All 15 patients(15/15,100%)undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period.In 22 cases of recurrence,ctDNA positivity was detected 22 times(22/22,100%)compared to 16 positives(16/22,73%)by imaging methods and 15 cases(15/22,68%)of elevated tumor markers.CONCLUSION ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.展开更多
文摘Molecular profiling of biliary tract cancers(BTCs)has paved the way for a broader range of therapeutic options,leading to improved survival outcomes.Given the challenges of tissue evaluation in BTCs,circulating tumor DNA(ct-DNA)has emerged as a promising non-invasive biomarker for genomic profiling.Bile has been proven to be a reliable ctDNA source,demonstrating higher concordance with tumor tissue than plasma.More importantly,ctDNA provides valuable insights into both clonal evolution and treatment response,including the detection of resistance mechanisms and mutation clearance,which are often associated with disease control.Although its role in recurrence monitoring remains investigational,early studies suggest that ctDNA detection may precede radiological recurrences.This review examines recent advancements in ctDNA analysis for patients with BTC,highlighting key developments,current clinical implications,and ongoing challenges.Large-scale prospective studies are needed to validate the clinical utility of ctDNA and to support its integration into BTC management.
基金supported by the National Cancer Institute of the National Institutes of Health under Award Number R00CA218603
文摘Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.
文摘Given the growing burden of colorectal cancer(CRC)as a global health challenge,it becomes imperative to focus on strategies that can mitigate its impact.Posttreatment surveillance has emerged as essential for early detection of recurrence,significantly improving patient outcomes.However,intensive surveillance strategies have shown mixed results compared to less intensive methods,emphasizing the necessity for personalized,risk-adapted approaches.The observed suboptimal adherence to existing surveillance protocols underscores the urgent need for more tailored and efficient strategies.In this context,circulating tumor DNA(ctDNA)emerges as a promising biomarker with significant potential to revolutionize post-treatment surveillance,demonstrating high specificity[0.95,95%confidence interval(CI):0.91-0.97]and robust diagnostic odds(37.6,95%CI:20.8-68.0)for recurrence detection.Furthermore,artificial intelligence and machine learning models integrating patient-specific and tumor features can enhance risk stratification and optimize surveillance strategies.The reported area under the receiver operating characteristic curve,measuring artificial intelligence model performance in predicting CRC recurrence,ranged from 0.581 and 0.593 at the lowest to 0.979 and 0.978 at the highest in training and validation cohorts,respectively.Despite this promise,addressing cost,accessibility,and extensive validation remains crucial for equitable integration into clinical practice.
基金Supported by Beijing Bethune Charitable Foundation and Provincial Natural Science Foundation of Liaoning,No.2022-MS-190.
文摘BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.
文摘Breast cancer remains a leading cause of cancer-related death in women worldwide.Emerging evidence highlights the central roles of breast cancer stem cells(BCSCs)and circulating tumor cells(CTCs)in tumor initiation,progression,therapeutic resistance,and metastasis.BCSCs self-renew and drive intertumoral heterogeneity,while CTCs disseminate from primary tumors into the bloodstream,seeding distant sites.These populations share molecular features,including stemness and epithelial-mesenchymal transition markers,supporting the concept that a subset of CTCs acquires stem-like traits,enhancing metastatic potential and resistance to standard therapies.This review synthesizes current knowledge on BCSC molecular programs,key signaling pathways(e.g.,Wnt,Notch,Hedgehog,Janus kinase/signal transducer and activator of transcription),and microenvironmental interactions that sustain stemness.It also examines mechanisms of CTC intravasation,state-dependent detection strategies,and their diagnostic and prognostic utility.We further highlight the adaptive plasticity of cancer stem celllike CTCs,their contributions to drug resistance,and opportunities to target these phenotypes for personalized treatment.Clarifying the biological links between BCSCs and CTCs could enable earlier detection of hidden metastasis and inform combination therapies aimed at both stemness and dissemination.As multimodal detection improves and functional profiling matures,integrating BCSC/CTC analyses into routine care may refine risk stratification and guide individualized management.
文摘Circulating tumor DNA(ctDNA)is the free DNA released by tumor or circulating tumor cells,which is associated with many tumor characteristics and can be used as a biomarker for early screening,monitoring,prognosis,and prediction of therapeutic response in patients with cancer.The field of gastric cancer is very attractive because there are no high-quality screening,monitoring,or prediction methods.Gastric cancer is characterized by great tumor heterogeneity,great differences in genetic and epigenetic characteristics among different subgroups of gastric cancer,and high sensitivity and specificity of methylated ctDNA,which is conducive to the identification of tumor genotypes and the formulation of accurate diagnostic and treatment strategies.In addition,many studies have confirmed that methylated DNA has unique advantages in predicting treatment response,adjuvant therapy,and drug resistance and can be used to increase the efficacy of chemotherapy regimens,improve the chemotherapy response of patients in the future,and even treat multidrug resistance.However,methylated ctDNA also faces many problems,such as low sensitivity and specificity in a single target,limited association between some gastric cancer subtypes and ctDNA,risk of off-target effects,and lack of large-sample and high-quality clinical research evidence.This review mainly summarizes the current research on the DNA methylation of circulating gastric cancer tumors and links these findings with the early screening of gastric cancer,recurrence monitoring,and potential treatment opportunities.With the advancement of technology and the deepening of cross-research between doctors and professionals,ctDNA detection will reveal more disease information and become an important basis for the field of gastric cancer and precision medicine treatment.
基金supported by the funding from National Natural Science Foundation of China(Nos.32025021,12374390,31971292,82072032,82202274)Ningbo 3315 Innovative Teams Program(No.2019A-14-C)+6 种基金The member of Youth Innovation Promotion Association Foundation of CAS(No.2023310)Key Scientific and Technological Special Project of Ningbo City(Nos.2023Z209,2020Z189)National Key R&D Program of China(No.2019YFA0405603)Provincial Natural Science Foundation of Zhejiang(Nos.LQ23H180007,LQ23H180003)Zhejiang Province Science and Technology Plan of Traditional Chinese Medicine(No.2021KY085)Zhejiang Provincial Traditional Chinese Medicine Foundation(No.2021ZB04)the Major Medical and Health Science and Technology Project of Zhejiang Province(No.WKJ-ZJ-2002)。
文摘Early diagnosis and accurate boundary delineation are the key steps of tumor precision medicine.Circulating tumor cells(CTCs)detection of liquid biopsy can provide abundant information for early diagnosis of cancer.High detection specificity and good enrichment features are two key factors for CTCs accurate identification in peripheral blood sample.For this purpose,iron oxide(IO)-based surface-enhanced Raman scattering(SERS)bioprobes with good biocompatibility,high detection sensitivity,remarkable detection specificity,and good enrichment efficiency,were developed for detecting different types of CTCs.Magnetic SERS bioprobes combined with programmed death ligand-1(PD-L1)antibody are regarded as an effective way to boost the targeting ability and detection specificity,benefiting for accurately capturing and identifying rare CTCs.Four types of CTCs with different PD-L1 expression were accurately distinguished among white blood cells via high-resolution SERS mapping images and stable Raman signals.Subsequently,CTCs blood samples obtained from the triple negative breast cancer patients were also successfully recognized compared to that of health people,indicating IO@AR@PDA-a PD-L1 SERS bioprobe possessed great potential for CTCs detection in liquid biopsy.Additionally,IO-based bioprobe exhibited excellent dual-modal imaging abilities of high-resolution SERS imaging mode and microimaging magnetic resonance imaging mode.These two highly complementary imaging modes endowed IO-based bioprobes unrivalled capacity in tumor boundary differentiation,supporting tumor accurate resection and precise surgery.To our best knowledge,this is the first time that biocompatible IO-based SERS bioprobes without noble metal element were reported not only for CTCs accurate detection,but also for precise tumor boundary delineation,showing great advantages in tumor diagnosis and treatment.
基金Supported by the Council for Science,Technology,and Innovation(CSTI)Cross-Ministerial Strategic Innovation Promotion Program(SIP)“Innovative AI Hospital System”(National Institute of Biomedical Innovation,Health and Nutrition),No.SIPAIH18C03the Japan Society for the Promotion of Science(JSPS)KAKENHI,No.JP19K09179 and No.JP23K08158.
文摘BACKGROUND Some patients with resectable or borderline resectable pancreatic ductal adenocarcinoma(PDAC)may have distant metastases,undetected on preoperative imaging or early recurrence,within 6 months after surgery.Occult metastases(OMs)must be accurately predicted to optimize multidisciplinary treatment.AIM To investigate the efficacy of circulating tumor DNA(ctDNA)in predicting OM.METHODS Two Japanese institutions prospectively collected preoperative plasma samples from PDAC patients between July 2019 and September 2021 and evaluated ctDNA using a targeted next-generation sequencing panel covering 52 cancer-related genes.RESULTS Among 135 PDAC patients,38 had OM and 35 were positive for ctDNA.The ctDNA positivity rate was significantly higher in patients with OM than in patients without OM.ctDNA-positive patients had significantly shorter median recurrence-free survival than ctDNA-negative patients.Logistic multivariate regression revealed ctDNA positivity as an independent predictor of OM.CONCLUSION Preoperative ctDNA in resectable PDAC is an independent predictor of OM and indicates poor prognosis following pancreatectomy and may be a useful biomarker in determining multidisciplinary patient care.
基金Supported by China Postdoctoral Science Foundation,No.2024M751334.
文摘BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer(GC)patients.To optimize treatment stratification and management,there is an urgent need for efficient and non-invasive biomarkers.A meta-analysis on the prognostic role of circulating tumor cells(CTCs)in GC revealed a strong association between CTCs and patient prognosis.Among CTC subtypes,Interstitial CTCs(I-CTCs)exhibited the strongest invasiveness.This study innovatively investigated the expression profile of I-CTCs in advanced GC patients to evaluate their clinical utility.AIM To evaluate the clinical utility of I-CTCs as a non-invasive prognostic biomarker in advanced GC.To investigate the correlation between I-CTC count thresholds and chemotherapy efficacy in advanced GC patients.To establish the potential of preoperative I-CTC profiling for optimizing treatment stratification and postoperative surveillance.METHODS This study retrospectively analyzed 59 patients with advanced GC treated at the General Surgery Clinical Medical Center of Gansu Provincial Hospital between October 2019 and October 2020.The expression levels of I-CTCs were measured,and patient survival was monitored.The receiver operating characteristic curve was plotted to determine the optimal cut-off value for I-CTCs expression levels.Based on this cut-off value,59 GC patients were grouped into positive and negative groups.The differences in clinicopathological characteristics between the two groups were analyzed.Patient survival was follow-up and recorded until October 2022.Plotting survival curves and performing univariate and multifactorial analyses of patient prognostic factors.The Kaplan-Meier method and Cox regression model were used,respectively.RESULTS A total of 59 patients were included in this study,and receiver operating characteristic curve analysis showed that the best cut-off value for I-CTCs was 5,with an area under the curve of 0.8356(95%CI:0.7122-0.9590).The I-CTC count of≥5 defines the positive group,while counts<5 are classified as the negative group.Positive I-CTCs correlated with the degree of tumor differentiation and disease progression(P<0.05).16 of 59 patients received neoadjuvant chemotherapy.There were divided into progressive disease and disease control groups based on response to neoadjuvant chemotherapy.Patients in the I-CTCs-negative group had longer overall survival and disease-free survival than those in the positive group(P<0.05).Multifactorial analysis revealed that I-CTCs positivity(HR=13.323,95%CI:1.675-105.962,P=0.014)was an independent risk factor for survival in patients with advanced GC.CONCLUSION In patients with advanced GC,an I-CTC count of≥5 is associated with both poor prognosis and reduced chemotherapy efficacy.I-CTCs may serve as a valuable preoperative biomarker for predicting the prognosis of advanced GC.
文摘Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is becoming more popular as a diagnostic tool in the clinical management of breast cancer.Elevated concentrations of these biomarkers during cancer treatment may be used as markers for cancer progression as well as to understand the mechanisms underlying metastasis and treatment resistance.Thus,these circulating markers serve as tools for cancer assessing and monitoring through a simple,non-invasive blood draw.However,despite several study results currently noting a potential clinical impact of ctDNA mutation tracking,the method is not used clinically in cancer diagnosis among patients and more studies are required to confirm it.This review focuses on understanding circulating tumor biomarkers,especially in breast cancer.
文摘BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always problematic.To use liquid biopsies clinically,it will be very important to address these questions.AIM To assess the origin of ctDNA,clarify the dynamics of ctDNA levels,assess ctDNA levels by using a xenograft mouse after treatment,and to determine whether tumor volume and invasion are related to ctDNA levels.METHODS Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell line.Groups of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA analysis.Analysis of ctDNA was performed by droplet digital PCR,using the human telomerase reverse transcriptase(hTERT)gene.RESULTS Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week 8.No hTERT was detected at week 4,but it was detected at week 8.However,in four-site xenograft mice,hTERT was detected both at week 4 and week 6.These experiments revealed that both tumor invasion and tumor volume were asso ciated with the detection of ctDNA.In resection experiments,hTERT was detected at resection,but had decreased by 6 h,and was no longer detected 1 and 3 d after resection.CONCLUSION We clarified the origin and dynamics of ctDNA,showing that tumor volume is an important factor.We also found that when the tumor was completely resected,ctDNA was absent after one or more days.
文摘Atypical fibroxanthomas (AFX) are rare skin tumors. These generally are superficial tumors, usually <3 cm red, fleshy, ulcerated skin lesions, that characteristically occur on sun-damaged skin, sometimes in immunocompromised or previously irradiated patients. These are part of a spectrum of more aggressive fibro-histiocytic neoplasms. In the older literature, these have been termed aggressive or metastatic AFX, but currently these have been reclassified as pleomorphic dermal sarcomas (PDS) and systemic undifferentiated pleomorphic sarcoma (UPS, formerly malignant fibrohistiocytic sarcoma, MFH). We present the case of a 64-year old woman who developed a deeply invasive PDS on the vertex of her scalp invading to the galea, with in-transit scalp metastases. Very little information is available about optimal treatment of metastatic PDS lesions. The patient was initially treated with 2 cycles of epirubicin/ifosfamide chemotherapy, resulting in life-threatening complications. A pretreatment peripheral blood sample was sent for CTC-derived colony assay. This sample grew 8 colonies from 10 ml blood. The tumor failed to respond to epirubicin and ifosfamide, and after several months of hospitalization, a second peripheral blood CTC-derived colony assay grew >376 colonies. The patient could not tolerate additional chemotherapy. She was therefore treated with the oral targeted agent pazopanib. The patient developed a dramatic biopsy-confirmed complete response. After 11 months of pazopanib treatment, a repeat CTC-derived culture sample grew only 8 colonies/10 ml blood. The complete response to pazopanib is still ongoing at over 41 months. To our knowledge, this is the first demonstration of clinical complete response of a PDS tumor following targeted therapy. An additional novel feature was the demonstration that CTC-derived colonies could be grown from the blood of a PDS patient. The number of colonies appeared to correlate with the clinical treatment response and seemed to function as a potential prognostic marker.
文摘Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biological information of tumor tissue,provide a new perspective and dimension for the study of tumor metastasis,progression,chemotherapy sensitivity and drug resistance.Cerebrospinal fluid(CSF)circulates through the ventricle and spinal cord cistern,which can better maintain the original information of tumor cells compared with the complicated environments of tissues and plasma.Study on the dynamic changes of CTCs in the CSF of the central nervous system(CNS)is relatively rare.However,the analysis of CTCs in CSF can be used to guide the treatment of gliomas and reveal the patho-physiological and genetic mechanisms of tumor cell metastasis to the CSF.This paper reviews the progress in the research on CTC detection in gliomas.
文摘Hepatocellular carcinoma(HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor. Therefore, to provide optimal treatment for each patient with HCC, more precise and effective biomarkers are urgently needed which could facilitate a more detailed individualized decision-making during HCC treatment, including the following; risk assessment, early cancer detection, prediction of treatment or prognostic outcome. In the blood of cancer patients, accumulating evidence about circulating tumor cells and cell-free nucleic acids has suggested their potent clinical utilities as novel biomarker. This concept, so-called "liquid biopsy" is widely known as an alternative approach to cancer tissue biopsy. This method might facilitate a more sensitive diagnosis and better decision-making by obtaining genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. In this article, we review recent developments based on the available literature on both circulating tumor cells and cell-free nucleic acids in cancer patients, especially focusing on Hepatocellular carcinoma.
基金Supported by Research project"CTC in gastrointestinal cancer"awarded by League Against Cancer Prague,Czech Republic and grant of the Czech Ministry of Health,No.IGA NT14439-3/2013the projects by Ministry of Helath Czech Republic,conceptual development of research organization,University Hospital Motol,Prague Czech Republic,No.000 64203
文摘AIM: To investigate the feasibility of separation and cultivation of circulating tumor cells (CTCs) in pancreatic cancer (PaC) using a filtration device.
文摘To improve the clinical outcomes of cancer patients, early detection and accurate monitoring of diseases are necessary. Numerous genetic and epigenetic alterations contribute to oncogenesis and cancer progression, and analyses of these changes have been increasingly utilized for diagnostic, prognostic and therapeutic purposes in malignant diseases including gastric cancer (GC). Surgical and/or biopsy specimens are generally used to understand the tumor-associated alterations; however, those approaches cannot always be performed because of their invasive characteristics and may fail to reflect current tumor dynamics and drug sensitivities, which may change during the therapeutic process. Therefore, the importance of developing a non-invasive biomarker with the ability to monitor real-time tumor dynamics should be emphasized. This concept, so called “liquid biopsy”, would provide an ideal therapeutic strategy for an individual cancer patient and would facilitate the development of “tailor-made” cancer management programs. In the blood of cancer patients, the presence and potent utilities of circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) such as DNA, mRNA and microRNA have been recognized, and their clinical relevance is attracting considerable attention. In this review, we discuss recent developments in this research field as well as the relevance and future perspectives of CTCs and cfNAs in cancer patients, especially focusing on GC.
文摘AIM To perform a meta-analysis of the related studies to assess whether circulating tumor cells(CTCs) can be used as a prognostic marker of esophageal cancer.METHODS Pub Med, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival(OS). The meta-analysis was performed using the random effects model, with hazard ratio(HR), risk ratio(RR) and 95% confidence intervals(95%CIs) as effect measures.RESULTS Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression(HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS(HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage(RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage(RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer.CONCLUSION Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted.
基金supported by Chinese National Natural Science Foundation (No. 81301323, 81472789)Beijing Natural Science Foundation (No. 7161002)the Capital Health Research and Development of Special (No. 2016-1-1021)
文摘Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients＇ clinical prognosis.Methods： The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment（SE） and immunostaining-fluorescence in situ hybridization（i FISH）platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.Results： CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 m L and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival（PFS） and overall survival（OS）. In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.Conclusions： Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.
基金Supported by the Ministry of Health of the Czech Republic,No.15-27939A
文摘BACKGROUND One of the most notable applications for circulating tumor DNA(ctDNA)detection in peripheral blood of patients with metastatic colorectal cancer(mCRC)is a long-term postoperative follow-up.Sometimes referred to as a“liquid(re)biopsy”it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals(months or even weeks).The presence of the disease and the actual extent of the tumor burden(tumor mass)within the patient’s body can be monitored.This is of particular importance,especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence.AIM To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer.METHODSA total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers.Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling.In addition to the baseline ctDNA testing prior to surgery,a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals.The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient.RESULTS Among the monitored patients,the R0(curative)resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures(26/28,93%).In the remaining cases of R0 surgeries that displayed ctDNA,both patients were diagnosed with a recurrence of the disease after 6 months.In 7 patients who underwent an R1 resection,4 ctDNA positivities(4/7,57%)were detected after surgery and associated with the confirmation of early disease recurrence(after 3 to 7 months).All 15 patients(15/15,100%)undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period.In 22 cases of recurrence,ctDNA positivity was detected 22 times(22/22,100%)compared to 16 positives(16/22,73%)by imaging methods and 15 cases(15/22,68%)of elevated tumor markers.CONCLUSION ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.
