BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition an...BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition and multi-target stool DNA(MT-sDNA)test in the diagnosis of CRC.METHODS We assessed the performance of the MT-sDNA test based on a hospital clinical trial.The intestinal microbiota was tested using 16S rRNA gene sequencing.This case-control study enrolled 54 CRC patients and 51 healthy controls.We identified biomarkers of bacterial structure,analyzed the relationship between different tumor markers and the relative abundance of related flora components,and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size,redundancy analysis,and random forest analysis.RESULTS MT-sDNA was associated with Bacteroides.MT-sDNA and carcinoembryonic antigen(CEA)were positively correlated with the existence of Parabacteroides,and alpha-fetoprotein(AFP)was positively associated with Faecalibacterium and Megamonas.In the random forest model,the existence of Streptococcus,Escherichia,Chitinophaga,Parasutterella,Lachnospira,and Romboutsia can distinguish CRC from health controls.The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%,with a sensitivity and specificity of 98.1%and 92.3%,respectively.CONCLUSION There is a positive correlation of MT-sDNA,CEA,and AFP with intestinal microbiome.Eight biomarkers including six genera of gut microbiota,MT-sDNA,and CEA showed a prominent sensitivity and specificity for CRC prediction,which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.展开更多
BACKGROUND Stool DNA(sDNA)methylation analysis is a promising,noninvasive approach for colorectal cancer screening;however,reliable biomarkers for detecting early-stage colon cancer(ECC)are lacking,particularly in the...BACKGROUND Stool DNA(sDNA)methylation analysis is a promising,noninvasive approach for colorectal cancer screening;however,reliable biomarkers for detecting early-stage colon cancer(ECC)are lacking,particularly in the Chinese population.AIM To identify a novel stool-based assay that can improve the effectiveness of ECC screening.METHODS A blinded case-control study was performed using archived stool samples from 125 ECC patients,and 125 control subjects with normal colonoscopy.The cohort was randomly divided into training and test sets at a 1.5:1 ratio.Targeted bisulfite sequencing(TBSeq)was conducted on five pairs of preoperative and postoperative sDNA samples from ECC patients to identify DNA methylation biomarkers,which were validated using pyrosequencing.By logistic regression analysis,a multiplex stool-based assay was developed in the training set,and the detection performance was further assessed in the test set and combined set.Theχ^(2)test was used to investigate the association of detection sensitivity with clinico-pathological features.RESULTS Following TBSeq,three hypermethylated cytosine-guanine sites were selected as biomarkers,including paired box 8,Ras-association domain family 1 and secreted frizzled-related protein 2,which differed between the groups and were involved in important cancer pathways.An sDNA panel containing the three biomarkers was constructed with a logistic model.Receiver operating characteristic(ROC)analysis revealed that this panel was superior to the fecal immunochemical test(FIT)or serum carcinoembryonic antigen for the detection of ECC.We further found that the combination of the sDNA panel with FIT could improve the screening effectiveness.In the combined set,the sensitivity,specificity and area under the ROC curve for this multiplex assay were 80.0%,93.6%and 0.918,respectively,and the performance remained excellent in the subgroup analysis by tumor stage.In addition,the detection sensitivity did not differ with tumor site,tumor stage,histological differentiation,age or sex,but was significantly higher in T4 than in T1-3 stage tumors(P=0.041).CONCLUSION We identified a novel multiplex stool-based assay combining sDNA methylation biomarkers and FIT,which could detect ECC with high sensitivity and specificity throughout the colon,showing a promising application perspective.展开更多
Objective:Stool DNA(sDNA)tests offer a noninvasive form of colon cancer screening for pa-tients,and although the test is expected to increase uptake of colon cancer screening,it is unknown if patients’perceptions of ...Objective:Stool DNA(sDNA)tests offer a noninvasive form of colon cancer screening for pa-tients,and although the test is expected to increase uptake of colon cancer screening,it is unknown if patients’perceptions of the sDNA test differ according to race and other patient characteristics.Methods:We conducted a self-administered survey of patients undergoing both a colonoscopy and an sDNA test to evaluate perceptions of sDNA testing.Results:Of the 613 participants who were sent surveys,423 responded(69%response rate).Respondents self-identified as African American(n=127,30%),Caucasian(n=284,67%),and other ethnicity(n=12,3%).In general,participants found the sDNA test more suitable than a colonos-copy(n=309,75%).In univariate analyses,a higher percentage of Caucasians as compared with African Americans found the sDNA test more suitable than a colonoscopy(89%vs.76%,p<0.01),and more Caucasians than African Americans preferred the sDNA test(43%vs.32%,p<0.05).Ad-justment for covariates reduced these racial differences to no significance.A family history of colo-rectal cancer remains a significant factor for patient’s preferences for screening regardless of race.Conclusions:Our study shows no racial differences in the perception of and preference for sDNA testing for colon screening.Intervention to increase the uptake of sDNA testing may help reduce racial disparities in colorectal cancer.展开更多
基金Supported by the Medical and Health Research Project of Zhejiang Province,No.2021KY1048 and 2022KY1142Ningbo Health Young Technical Backbone Talents Training Program,No.2020SWSQNGG-02the Key Science and Technology Project of Ningbo City,No.2021Z133.
文摘BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition and multi-target stool DNA(MT-sDNA)test in the diagnosis of CRC.METHODS We assessed the performance of the MT-sDNA test based on a hospital clinical trial.The intestinal microbiota was tested using 16S rRNA gene sequencing.This case-control study enrolled 54 CRC patients and 51 healthy controls.We identified biomarkers of bacterial structure,analyzed the relationship between different tumor markers and the relative abundance of related flora components,and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size,redundancy analysis,and random forest analysis.RESULTS MT-sDNA was associated with Bacteroides.MT-sDNA and carcinoembryonic antigen(CEA)were positively correlated with the existence of Parabacteroides,and alpha-fetoprotein(AFP)was positively associated with Faecalibacterium and Megamonas.In the random forest model,the existence of Streptococcus,Escherichia,Chitinophaga,Parasutterella,Lachnospira,and Romboutsia can distinguish CRC from health controls.The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%,with a sensitivity and specificity of 98.1%and 92.3%,respectively.CONCLUSION There is a positive correlation of MT-sDNA,CEA,and AFP with intestinal microbiome.Eight biomarkers including six genera of gut microbiota,MT-sDNA,and CEA showed a prominent sensitivity and specificity for CRC prediction,which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.
基金Supported by Shanghai Pujiang Program,No. 21PJD066Shanghai Municipal Commission of Health and Family Planning,No. ZK2019A19+1 种基金Shanghai Municipal Science and Technology Commission,No. 19411971500Shanghai Yangpu District Science and Technology Commission,No. YPM202101
文摘BACKGROUND Stool DNA(sDNA)methylation analysis is a promising,noninvasive approach for colorectal cancer screening;however,reliable biomarkers for detecting early-stage colon cancer(ECC)are lacking,particularly in the Chinese population.AIM To identify a novel stool-based assay that can improve the effectiveness of ECC screening.METHODS A blinded case-control study was performed using archived stool samples from 125 ECC patients,and 125 control subjects with normal colonoscopy.The cohort was randomly divided into training and test sets at a 1.5:1 ratio.Targeted bisulfite sequencing(TBSeq)was conducted on five pairs of preoperative and postoperative sDNA samples from ECC patients to identify DNA methylation biomarkers,which were validated using pyrosequencing.By logistic regression analysis,a multiplex stool-based assay was developed in the training set,and the detection performance was further assessed in the test set and combined set.Theχ^(2)test was used to investigate the association of detection sensitivity with clinico-pathological features.RESULTS Following TBSeq,three hypermethylated cytosine-guanine sites were selected as biomarkers,including paired box 8,Ras-association domain family 1 and secreted frizzled-related protein 2,which differed between the groups and were involved in important cancer pathways.An sDNA panel containing the three biomarkers was constructed with a logistic model.Receiver operating characteristic(ROC)analysis revealed that this panel was superior to the fecal immunochemical test(FIT)or serum carcinoembryonic antigen for the detection of ECC.We further found that the combination of the sDNA panel with FIT could improve the screening effectiveness.In the combined set,the sensitivity,specificity and area under the ROC curve for this multiplex assay were 80.0%,93.6%and 0.918,respectively,and the performance remained excellent in the subgroup analysis by tumor stage.In addition,the detection sensitivity did not differ with tumor site,tumor stage,histological differentiation,age or sex,but was significantly higher in T4 than in T1-3 stage tumors(P=0.041).CONCLUSION We identified a novel multiplex stool-based assay combining sDNA methylation biomarkers and FIT,which could detect ECC with high sensitivity and specificity throughout the colon,showing a promising application perspective.
基金the National Cancer Institute(R01 CA136726 and U01CA181770 to L.Li,and P50CA50964 to L.Li and G.Cooper).
文摘Objective:Stool DNA(sDNA)tests offer a noninvasive form of colon cancer screening for pa-tients,and although the test is expected to increase uptake of colon cancer screening,it is unknown if patients’perceptions of the sDNA test differ according to race and other patient characteristics.Methods:We conducted a self-administered survey of patients undergoing both a colonoscopy and an sDNA test to evaluate perceptions of sDNA testing.Results:Of the 613 participants who were sent surveys,423 responded(69%response rate).Respondents self-identified as African American(n=127,30%),Caucasian(n=284,67%),and other ethnicity(n=12,3%).In general,participants found the sDNA test more suitable than a colonos-copy(n=309,75%).In univariate analyses,a higher percentage of Caucasians as compared with African Americans found the sDNA test more suitable than a colonoscopy(89%vs.76%,p<0.01),and more Caucasians than African Americans preferred the sDNA test(43%vs.32%,p<0.05).Ad-justment for covariates reduced these racial differences to no significance.A family history of colo-rectal cancer remains a significant factor for patient’s preferences for screening regardless of race.Conclusions:Our study shows no racial differences in the perception of and preference for sDNA testing for colon screening.Intervention to increase the uptake of sDNA testing may help reduce racial disparities in colorectal cancer.
