AIM： To quantify the circulating DNA in plasma from patients with hepatocellular carcinoma （HCC） and to evaluate its prognostic value. METHODS： Blood samples were collected from 79 patients with HCC before operati...AIM： To quantify the circulating DNA in plasma from patients with hepatocellular carcinoma （HCC） and to evaluate its prognostic value. METHODS： Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. Circulating DNA was extracted from plasma and quantified. The association between circulating DNA level and prognosis of HCC patients was evaluated. RESULTS： Compared with the healthy volunteers （17.6 ± 9.5 ng/mL）, a significant higher circulating DNA level was found in the patients with HCC （47.1 ± 43.7 ng/ mL, P = 0.000） or with liver cirrhosis （30.0 ± 13.3 ng/ mL, P = 0.002）. The circulating DNA level was closely associated with tumor size （P = 0.008） and TNM stage （P = 0.040）, negatively associated with the 3-year diseasefree survival （DFS） （P = 0.017） and overall survival （OS） （P = 0.001）. CONCLUSION： Large or invasive tumor may release more circulating DNA, and higher level of circulating DNA may be associated with poor prognosis of HCC patients.展开更多
In this paper, we first presented a novel method for quantification of circulating DNA in human serum based on capillary zone electrophoresis with laser-induced fluorescence detection (CZE-LIF). The serum was digeste...In this paper, we first presented a novel method for quantification of circulating DNA in human serum based on capillary zone electrophoresis with laser-induced fluorescence detection (CZE-LIF). The serum was digested by proteinase to release free DNA, and then CZE-LIF system was used for the quantification of total circulating DNA. This method was successfully used to quantify the circulating DNA levels in sera from healthy individuals and certain cancer patients. We found the significantly elevated circulating DNA levels in certain prostate cancer patients. Our results demonstrated that CZE-LIF system has good linearity, excellent sensitivity (0.5 ng/mL DNA), satisfactory reproducibility (RSDs in one day and between days were both less than 5%) and reliability, and is well suitable to the quantification of the circulating DNA in human serum or plasma.展开更多
Colorectal cancer(CRC) is one of the most prevalent malignancies in the world. CRC-associated morbidity and mortality is continuously increasing, in part due to a lack of early detection. The existing screening tools ...Colorectal cancer(CRC) is one of the most prevalent malignancies in the world. CRC-associated morbidity and mortality is continuously increasing, in part due to a lack of early detection. The existing screening tools such as colonoscopy, are invasive and yet high cost, affecting the willingness of patients to participate in screening programs. In recent years, evidence is accumulating that the interaction of aberrant genetic and epigenetic modifications is the cornerstone for the CRC development and progression by alternating the function of tumor suppressor genes, DNA repair genes and oncogenes of colonic cells. Apart from the understanding of the underlying mechanism(s) of carcinogenesis, the aforementioned interaction has also allowed identification of clinical biomarkers, especially epigenetic, for the early detection and prognosis of cancer patients. One of the ways to detect these epigenetic biomarkers is the cell-free circulating DNA(circ DNA), a blood-based cancer diagnostic test, mainly focusing in the molecular alterations found in tumor cells, such as DNA mutations and DNA methylation.In this brief review, we epitomize the current knowledge on the research in circ DNA biomarkers-mainly focusing on DNA methylation-as potential blood-based tests for early detection of colorectal cancer and the challenges for validation and globally implementation of this emergent technology.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
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
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
Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential biomarker in colorectal cancer(CRC)patients.However,the role of ctDNA in CRC prognosis prediction remains unclear.The objective is to sys...Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential biomarker in colorectal cancer(CRC)patients.However,the role of ctDNA in CRC prognosis prediction remains unclear.The objective is to systematically assess the clinical value of ctDNA in colorectal cancer prognosis prediction throughout the treatment cycle.Methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov database was searched from January 2016 to April 2023.Observational studies and randomized clinical trials reporting on ctDNA and prognostic outcomes in CRC patients were included.Pooled hazard risk ratios(HRs)were calculated for the primary outcomes,relapse-free survival(RFS),and overall survival(OS).Random-effects models were preferred considering the potential heterogeneity.Results:Sixty-five cohort studies were included.Association between ctDNA and shorter RFS or OS was significant,especially after the full-course treatment recommended by the guidelines(HR=8.92[95%CI:6.02-13.22],P<0.001,I^(2)=73%;HR=3.05[95%CI:1.72-5.41],P<0.001,I^(2)=48%)for all types of CRC patients.Despite the presence of heterogeneity,subgroup analyses showed that the cancer type and ctDNA detection assays may be the underlying cause.Besides,ctDNA may detect recurrence earlier than radiographic progression,but no uniform sampling time point between studies might bring bias.However,ctDNA detection did not appear to correlate with pathological complete response achievement in patients with locally advanced rectal cancer.Conclusion:ctDNA detection was significantly associated with poorer prognosis.The potential applications in prognostic prediction are promising and remain to be evaluated in other fields.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
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
Objective:Circulating tumor DNA(ctDNA)has shown potential as a prognostic biomarker in patients with solid tumors.This study aimed to systematically summarize the global application of ctDNA in the prognostic man-agem...Objective:Circulating tumor DNA(ctDNA)has shown potential as a prognostic biomarker in patients with solid tumors.This study aimed to systematically summarize the global application of ctDNA in the prognostic man-agement of solid tumor patients and to evaluate the quality of the current studies.Methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov databases were searched to collect cohort studies on ctDNA in the prognosis of solid tumor patients from January 2016 to May 2022.The language was limited to English.Information including general information,participants and cancer characteristics,ctDNA and outcome information were extracted.The quality of the studies was assessed using the Newcastle-Ottawa Scale checklist.Results:A total of 214 studies were included in the final analysis,encompassing 21,076 patients.The number of studies has increased annually from 2016 to 2022.The most common types of solid tumors studied were colorectal cancer(27.10%),lung cancer(20.09%),pancreatic cancer(16.82%),and breast cancer(14.02%).The top three journals by number of publications had an impact factor in 2023 greater than 10.Of the studies,the median sample size was 69(interquartile range:41-111),69.81%had a sample size<100,68.92%had a median/mean age≥60 years,and 74.05%were from developed countries.Multi-center studies accounted for 40.36%.Additionally,29.82%of the studies had a bias risk score≤6.Only 16.67%of studies on liver cancer had a bias risk score>6.The primary criteria not met by the studies included“Adequacy of follow-up of cohorts”(33.33%),“Assessment of outcome”(32.16%)and“Representativeness of the exposed cohort”(27.49%).Conclusions:The prognostic value of ctDNA in patients with solid tumors is gaining increasing attention,leading to a steady rise in the number of studies.However,many studies still suffer from small sample sizes and a lack of representativeness.Furthermore,details regarding ctDNA detection methods and results reporting are often insufficiently described.There is an urgent need to improve the quality of such research.展开更多
The detection of circulating tumor DNA(ctDNA)with high sensitivity and specificity is crucial for the early diagnosis and monitoring of tumors,as well as for drug therapy.In this study,a simple and highly sensitive bi...The detection of circulating tumor DNA(ctDNA)with high sensitivity and specificity is crucial for the early diagnosis and monitoring of tumors,as well as for drug therapy.In this study,a simple and highly sensitive biosensor was specifically designed for the identification of targeted ctDNA.For the first time,a three-dimensional polyvinylidene fluoride-graphene oxide-chitosan(PVDF/CS/GO)nanofiber mesh was fabricated on a polydimethylsiloxane(PDMS)micropillar substrate using electrospinning technology,and the nanofibers were functionalized with peptide nucleic acids probe-gold nanoparticle(PNA-AuNP)complexes,which served as affinity molecules for detecting the methylation of the E542K variant of the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α(PIK3CA)gene in the peripheral blood of cancer patients.Additionally,an anti-5-Methylcytosine monoclonal antibody-multi-walled carbon nanotubes-COOH complex(Anti-5-mC-MWCNTs-COOH)complex was incubated to result in significantly amplified electrochemical signals for the accurate quantification of the E542K variant of the PIK3CA gene.Detectable signal responses were observed only when both molecules were simultaneously present,greatly enhancing the accuracy of the analysis.The biosensor exhibits high capture sensitivity for the methylation level of the E542K variant of the PIK3CA gene across a concentration range of 50 to 10000 fmol/L,with the lowest detection limit of 10 fmol/L.The ctDNA nanobiosensor has been shown to be both feasible and valuable for quantifying ctDNA concentrations in clinical blood samples.Consequently,this 3D nanofiber biosensor shows significant potential for clinical applications in cancer diagnosis and personalized medical treatments.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
Objectives:Elevated circulating DNA(cirDNA)concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA release.We carried o...Objectives:Elevated circulating DNA(cirDNA)concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA release.We carried out the first prospective,multicenter study of the dynamics of cirDNA and neutrophil extracellular trap(NETs)markers during the perioperative period from 24 h before surgery up to 72 h after curative surgery in cancer patients.Methods:We examined the plasma levels of two NETs protein markers[myeloperoxidase(MPO)and neutrophil elastase(NE)],as well as levels of cirDNA of nuclear(cir-nDNA)and mitochondrial(cir-mtDNA)origin in 29 colon,prostate,and breast cancer patients and in 114 healthy individuals(HI).Results:The synergistic analytical information provided by these markers revealed that:(i)NETs formation contributes to post-surgery conditions;(i)post-surgery cir-nDNA levels were highly associated with NE and MPO in colon cancer[r=0.60(P<0.001)and r=0.53(P<0.01),respectivelyl,but not in prostate and breast cancer;(i)each tumor type shows a specific pattern of cir-nDNA and NETs marker dynamics,but overall the pre-and post-surgery median values of cir-nDNA,NE,and MPO were significantly higher in cancer patients than in HI.Conclusion:Taken as a whole,our work reveals the association of NETs formation with the elevated cir-nDNA release during a cancer patient's perioperative period,depending on surgical procedure or cancer type.By contrast,cir-mtDNA is poorly associated with NETs formation in the studied perioperative period,which would appear to indicate a different mechanism of release or suggest mitochondrial dysfunction.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
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
With the rapid development of science and technology,cell-free DNA(cfDNA)is rapidly becoming an important biomarker for tumor diagnosis,monitoring and prognosis,and this cfDNA-based liquid biopsy technology has great ...With the rapid development of science and technology,cell-free DNA(cfDNA)is rapidly becoming an important biomarker for tumor diagnosis,monitoring and prognosis,and this cfDNA-based liquid biopsy technology has great potential to become an important part of precision medicine.cfDNA is the total amount of free DNA in the systemic circulation,including DNA fragments derived from tumor cells and all other somatic cells.Tumor cells release fragments of DNA into the bloodstream,and this source of cfDNA is called circulating tumor DNA(ctDNA).cfDNA detection has become a major focus in the field of tumor research in recent years,which provides a new opportunity for non-invasive diagnosis and prognosis of cancer.In this paper,we discuss the limitations of the study on the origin and dynamics analysis of ctDNA,and how to solve these problems in the future.Although the future faces major challenges,it also con-tains great potential.展开更多
Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Rece...Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.展开更多
For many years tissue biopsy has been the primary procedure to establish cancer diagnosis and determine further treatment and prognosis.However,this method has multiple drawbacks,including,to mention some,being an inv...For many years tissue biopsy has been the primary procedure to establish cancer diagnosis and determine further treatment and prognosis.However,this method has multiple drawbacks,including,to mention some,being an invasive procedure carrying significant risk for fragile patients and allowing only for a“snapshot”of the tumor biology in time.The process of liquid biopsy allows for a minimally invasive procedure that provides molecular information about underlying cancer by analyzing circulating tumor DNA(ctDNA)via next-generation sequencing technology and circulating tumor cells.This paper focuses on describing the basis of ctDNA and its current utilities.展开更多
Analysis of patient＇s materials like cells or nucleic acids obtained in a minimally invasive or noninvasive manner through the sampling of blood or other body fluids serves as liquid biopsies, which has huge potentia...Analysis of patient＇s materials like cells or nucleic acids obtained in a minimally invasive or noninvasive manner through the sampling of blood or other body fluids serves as liquid biopsies, which has huge potential for numerous diagnostic applications. Circulating cell-free DNA（cfDNA） is explored as a prognostic or predictive marker of liquid biopsies with the improvements in genomic and molecular methods. DNA methylation is an important epigenetic marker known to affect gene expression. cfDNA methylation detection is a very promising approach as abnormal distribution of DNA methylation is one of the hallmarks of many cancers and methylation changes occur early during carcinogenesis. This re？view summarizes the various investigational applications of cfDNA methylation and its oxidized de？rivatives as biomarkers for cancer diagnosis, prenatal diagnosis and organ transplantation monitoring.The review also provides a brief overview of the technologies for cfDNA methylation analysis based on next generation sequencing.展开更多
基金Supported by the National Science Fund for Distinguished Young Scholars, No. 30325041General Program of National Natural Science Foundation of China, No. 30371378Key Program Project of National Natural Science Foundation of China, No. 30430720Key Program Project of Shanghai Science Technology Committee, No. 04JC14028
文摘AIM： To quantify the circulating DNA in plasma from patients with hepatocellular carcinoma （HCC） and to evaluate its prognostic value. METHODS： Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. Circulating DNA was extracted from plasma and quantified. The association between circulating DNA level and prognosis of HCC patients was evaluated. RESULTS： Compared with the healthy volunteers （17.6 ± 9.5 ng/mL）, a significant higher circulating DNA level was found in the patients with HCC （47.1 ± 43.7 ng/ mL, P = 0.000） or with liver cirrhosis （30.0 ± 13.3 ng/ mL, P = 0.002）. The circulating DNA level was closely associated with tumor size （P = 0.008） and TNM stage （P = 0.040）, negatively associated with the 3-year diseasefree survival （DFS） （P = 0.017） and overall survival （OS） （P = 0.001）. CONCLUSION： Large or invasive tumor may release more circulating DNA, and higher level of circulating DNA may be associated with poor prognosis of HCC patients.
文摘In this paper, we first presented a novel method for quantification of circulating DNA in human serum based on capillary zone electrophoresis with laser-induced fluorescence detection (CZE-LIF). The serum was digested by proteinase to release free DNA, and then CZE-LIF system was used for the quantification of total circulating DNA. This method was successfully used to quantify the circulating DNA levels in sera from healthy individuals and certain cancer patients. We found the significantly elevated circulating DNA levels in certain prostate cancer patients. Our results demonstrated that CZE-LIF system has good linearity, excellent sensitivity (0.5 ng/mL DNA), satisfactory reproducibility (RSDs in one day and between days were both less than 5%) and reliability, and is well suitable to the quantification of the circulating DNA in human serum or plasma.
文摘Colorectal cancer(CRC) is one of the most prevalent malignancies in the world. CRC-associated morbidity and mortality is continuously increasing, in part due to a lack of early detection. The existing screening tools such as colonoscopy, are invasive and yet high cost, affecting the willingness of patients to participate in screening programs. In recent years, evidence is accumulating that the interaction of aberrant genetic and epigenetic modifications is the cornerstone for the CRC development and progression by alternating the function of tumor suppressor genes, DNA repair genes and oncogenes of colonic cells. Apart from the understanding of the underlying mechanism(s) of carcinogenesis, the aforementioned interaction has also allowed identification of clinical biomarkers, especially epigenetic, for the early detection and prognosis of cancer patients. One of the ways to detect these epigenetic biomarkers is the cell-free circulating DNA(circ DNA), a blood-based cancer diagnostic test, mainly focusing in the molecular alterations found in tumor cells, such as DNA mutations and DNA methylation.In this brief review, we epitomize the current knowledge on the research in circ DNA biomarkers-mainly focusing on DNA methylation-as potential blood-based tests for early detection of colorectal cancer and the challenges for validation and globally implementation of this emergent technology.
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.
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.
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funded by the Capital’s Funds for Health Improve-ment and Research(grant number:2024-1G-4023)the Special Project for Director,China Center for Evidence Based Traditional Chinese Medicine(grant number:2020YJSZX-2)National Natural Science Foundation of China(grant number:72474008).
文摘Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential biomarker in colorectal cancer(CRC)patients.However,the role of ctDNA in CRC prognosis prediction remains unclear.The objective is to systematically assess the clinical value of ctDNA in colorectal cancer prognosis prediction throughout the treatment cycle.Methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov database was searched from January 2016 to April 2023.Observational studies and randomized clinical trials reporting on ctDNA and prognostic outcomes in CRC patients were included.Pooled hazard risk ratios(HRs)were calculated for the primary outcomes,relapse-free survival(RFS),and overall survival(OS).Random-effects models were preferred considering the potential heterogeneity.Results:Sixty-five cohort studies were included.Association between ctDNA and shorter RFS or OS was significant,especially after the full-course treatment recommended by the guidelines(HR=8.92[95%CI:6.02-13.22],P<0.001,I^(2)=73%;HR=3.05[95%CI:1.72-5.41],P<0.001,I^(2)=48%)for all types of CRC patients.Despite the presence of heterogeneity,subgroup analyses showed that the cancer type and ctDNA detection assays may be the underlying cause.Besides,ctDNA may detect recurrence earlier than radiographic progression,but no uniform sampling time point between studies might bring bias.However,ctDNA detection did not appear to correlate with pathological complete response achievement in patients with locally advanced rectal cancer.Conclusion:ctDNA detection was significantly associated with poorer prognosis.The potential applications in prognostic prediction are promising and remain to be evaluated in other fields.
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.
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funded by the National Natural Science Foundation of China(grant numbers:72474008,72074011)the Capital’s Funds for Health Improvement and Research(grant number:2024-1G-4023)the Special Project for Director,China Center for Evidence Based Traditional Chinese Medicine(grant number:2020YJSZX-2).
文摘Objective:Circulating tumor DNA(ctDNA)has shown potential as a prognostic biomarker in patients with solid tumors.This study aimed to systematically summarize the global application of ctDNA in the prognostic man-agement of solid tumor patients and to evaluate the quality of the current studies.Methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov databases were searched to collect cohort studies on ctDNA in the prognosis of solid tumor patients from January 2016 to May 2022.The language was limited to English.Information including general information,participants and cancer characteristics,ctDNA and outcome information were extracted.The quality of the studies was assessed using the Newcastle-Ottawa Scale checklist.Results:A total of 214 studies were included in the final analysis,encompassing 21,076 patients.The number of studies has increased annually from 2016 to 2022.The most common types of solid tumors studied were colorectal cancer(27.10%),lung cancer(20.09%),pancreatic cancer(16.82%),and breast cancer(14.02%).The top three journals by number of publications had an impact factor in 2023 greater than 10.Of the studies,the median sample size was 69(interquartile range:41-111),69.81%had a sample size<100,68.92%had a median/mean age≥60 years,and 74.05%were from developed countries.Multi-center studies accounted for 40.36%.Additionally,29.82%of the studies had a bias risk score≤6.Only 16.67%of studies on liver cancer had a bias risk score>6.The primary criteria not met by the studies included“Adequacy of follow-up of cohorts”(33.33%),“Assessment of outcome”(32.16%)and“Representativeness of the exposed cohort”(27.49%).Conclusions:The prognostic value of ctDNA in patients with solid tumors is gaining increasing attention,leading to a steady rise in the number of studies.However,many studies still suffer from small sample sizes and a lack of representativeness.Furthermore,details regarding ctDNA detection methods and results reporting are often insufficiently described.There is an urgent need to improve the quality of such research.
基金Funded by the National Natural Science Foundation of China(No.11804121)Special Funds for Central Guiding Local Scientific and Technological Development Project(No.2016ZYYD049)。
文摘The detection of circulating tumor DNA(ctDNA)with high sensitivity and specificity is crucial for the early diagnosis and monitoring of tumors,as well as for drug therapy.In this study,a simple and highly sensitive biosensor was specifically designed for the identification of targeted ctDNA.For the first time,a three-dimensional polyvinylidene fluoride-graphene oxide-chitosan(PVDF/CS/GO)nanofiber mesh was fabricated on a polydimethylsiloxane(PDMS)micropillar substrate using electrospinning technology,and the nanofibers were functionalized with peptide nucleic acids probe-gold nanoparticle(PNA-AuNP)complexes,which served as affinity molecules for detecting the methylation of the E542K variant of the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α(PIK3CA)gene in the peripheral blood of cancer patients.Additionally,an anti-5-Methylcytosine monoclonal antibody-multi-walled carbon nanotubes-COOH complex(Anti-5-mC-MWCNTs-COOH)complex was incubated to result in significantly amplified electrochemical signals for the accurate quantification of the E542K variant of the PIK3CA gene.Detectable signal responses were observed only when both molecules were simultaneously present,greatly enhancing the accuracy of the analysis.The biosensor exhibits high capture sensitivity for the methylation level of the E542K variant of the PIK3CA gene across a concentration range of 50 to 10000 fmol/L,with the lowest detection limit of 10 fmol/L.The ctDNA nanobiosensor has been shown to be both feasible and valuable for quantifying ctDNA concentrations in clinical blood samples.Consequently,this 3D nanofiber biosensor shows significant potential for clinical applications in cancer diagnosis and personalized medical treatments.
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.
基金grant NIMAO 2016-08 and partiallyysupportedbySIRIC MontpellieCr ancerGrant INCa_Inserm_DGOS_12553 and the"SociétéFrancaise des acides nucléiques circulants"(SFAC).The promotor of this study is the Centre Hospitalier Universitaire de Nimes.The authors thank Cormac Mc Carthy(Mc Carthy Consultant,Montpellier)for English editing(financial compensation).We thank our patients and their families for their trustand all the participating physicians and supporting staff.We thank all healthy donors who participated in this study.We also thank the clinical investigators of the centers who participated in this study.
文摘Objectives:Elevated circulating DNA(cirDNA)concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA release.We carried out the first prospective,multicenter study of the dynamics of cirDNA and neutrophil extracellular trap(NETs)markers during the perioperative period from 24 h before surgery up to 72 h after curative surgery in cancer patients.Methods:We examined the plasma levels of two NETs protein markers[myeloperoxidase(MPO)and neutrophil elastase(NE)],as well as levels of cirDNA of nuclear(cir-nDNA)and mitochondrial(cir-mtDNA)origin in 29 colon,prostate,and breast cancer patients and in 114 healthy individuals(HI).Results:The synergistic analytical information provided by these markers revealed that:(i)NETs formation contributes to post-surgery conditions;(i)post-surgery cir-nDNA levels were highly associated with NE and MPO in colon cancer[r=0.60(P<0.001)and r=0.53(P<0.01),respectivelyl,but not in prostate and breast cancer;(i)each tumor type shows a specific pattern of cir-nDNA and NETs marker dynamics,but overall the pre-and post-surgery median values of cir-nDNA,NE,and MPO were significantly higher in cancer patients than in HI.Conclusion:Taken as a whole,our work reveals the association of NETs formation with the elevated cir-nDNA release during a cancer patient's perioperative period,depending on surgical procedure or cancer type.By contrast,cir-mtDNA is poorly associated with NETs formation in the studied perioperative period,which would appear to indicate a different mechanism of release or suggest mitochondrial dysfunction.
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.
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.
基金Supported by Talent Scientific Research Start-up Foundation of Wannan Medical College,No.WYRCQD2023045.
文摘With the rapid development of science and technology,cell-free DNA(cfDNA)is rapidly becoming an important biomarker for tumor diagnosis,monitoring and prognosis,and this cfDNA-based liquid biopsy technology has great potential to become an important part of precision medicine.cfDNA is the total amount of free DNA in the systemic circulation,including DNA fragments derived from tumor cells and all other somatic cells.Tumor cells release fragments of DNA into the bloodstream,and this source of cfDNA is called circulating tumor DNA(ctDNA).cfDNA detection has become a major focus in the field of tumor research in recent years,which provides a new opportunity for non-invasive diagnosis and prognosis of cancer.In this paper,we discuss the limitations of the study on the origin and dynamics analysis of ctDNA,and how to solve these problems in the future.Although the future faces major challenges,it also con-tains great potential.
基金supported by National Natural Science Foundation of China (No. 31902287)Key R&D and Promotion Projects of Henan Province (No. 242102310467, No. 242102310240 and No. 23210 2310132)Henan Department of Public Health (No. LHGJ20221021)。
文摘Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.
文摘For many years tissue biopsy has been the primary procedure to establish cancer diagnosis and determine further treatment and prognosis.However,this method has multiple drawbacks,including,to mention some,being an invasive procedure carrying significant risk for fragile patients and allowing only for a“snapshot”of the tumor biology in time.The process of liquid biopsy allows for a minimally invasive procedure that provides molecular information about underlying cancer by analyzing circulating tumor DNA(ctDNA)via next-generation sequencing technology and circulating tumor cells.This paper focuses on describing the basis of ctDNA and its current utilities.
基金supported by grants from the National Basic Research Program of China(MOST2016YFC0900301 and 2014CB964900)the National Natural Science Foundation of China(No. 91519325)the Beijing Natural Science Foundation (No. 5162012)
文摘Analysis of patient＇s materials like cells or nucleic acids obtained in a minimally invasive or noninvasive manner through the sampling of blood or other body fluids serves as liquid biopsies, which has huge potential for numerous diagnostic applications. Circulating cell-free DNA（cfDNA） is explored as a prognostic or predictive marker of liquid biopsies with the improvements in genomic and molecular methods. DNA methylation is an important epigenetic marker known to affect gene expression. cfDNA methylation detection is a very promising approach as abnormal distribution of DNA methylation is one of the hallmarks of many cancers and methylation changes occur early during carcinogenesis. This re？view summarizes the various investigational applications of cfDNA methylation and its oxidized de？rivatives as biomarkers for cancer diagnosis, prenatal diagnosis and organ transplantation monitoring.The review also provides a brief overview of the technologies for cfDNA methylation analysis based on next generation sequencing.
