Detection Of Fecal DNA Methylation For Colorectal Neoplasia Screening: A Meta-analysis

AIM: To systemically evaluate the feasibility of using aberrant methylation of genes as biomarkers for the detection of colorectal neoplasia.METHODS: We searched PubMed,MEDLINE,CNKI,wanfang and VIP to collect the diagnostic trials on the aberrant methylation of genes in stool for the detection of colorectal cancer or adenomas with the key words“colorectal cancer/ colorectal adenoma”,“methylation”,“stool/ fecal DNA”for studies that published from 2007 to 2017.and we excluding relevant documents that do not meet the inclusion criteria,QUADAS-2 items were used to evaluate the quality of the included studies,we used the Stata statistical software(version 15.0)to perform statistical analyses.RESULTS: A total of 38 studies including 4958 patients were selected into the final analysis.The results of meta-analysis showed that,The weighted sensitivity,specificity,DLR positive,DLR negative,diagnostic score,diagnostic odds ratio(DOR),area under the summary receiver operating characteristic(SROC)curve of single methylated genes in fecal DNA for the detection of colorectal cancer,adenomas and colorectal neoplasia were 0.74[95%CI:0.68-0.78]、0.46[95%CI:0.33-0.59]、0.66[95%CI:0.59-0.72];0.92[95%CI:0.87-0.94]、0.91[95% CI:0.87-0.94]、0.91[95%CI:0.87-0.94],8.74[95%CI:5.79-13.20]、5.02[95%CI:3.02-8.36]、7.47[95%CI:4.99-11.18],0.29[95%CI:0.24-0.35]、0.60[95%CI:0.47-0.76]、0.38[95%CI:0.31-0.46],3.41[95%CI:2.90-3.92]、2.13[95%CI:1.41-2.85]、2.99[95%CI:2.47-3.51],30.34[95%CI:18.18-50.61]、8.41[95%CI:4.11-17.24]、19.89[11.81-33.52],0.90 [95%CI:0.87-0.92]、0.90 [95%CI:0.87-0.92]、 0.89 [95%CI : 0.86-0.91] respectively.The weighted sensitivity,specificity,DLR positive,DLR negative,diagnostic score,diagnostic odds ratio(DOR),area under the summary receiver operating characteristic(SROC)curve of multiple methylated genes were 0.86[95%CI:0.81-0.89]、0.64[95%CI:0.58-0.70]、0.81[95%CI:0.75-0.85],0.88[95%CI:0.83-0.92]、0.90[95%CI:0.85-0.94]、0.89[95%CI:0.83-0.92],7.41[95%CI:5.17-10.63]、6.71[95%CI:4.24-10.63]、7.03[95%CI:4.89-10.11],0.16[95%CI:0.12-0.22]、0.40[95%CI:0.34-0.47]、0.22[95%CI:0.17-0.28],3.82[95%CI:3.39-4.25]、2.83[95%CI:2.31-3.35]、3.47[95%CI:3.04-3.90],45.69[95%CI:29.64-70.43]、16.94[95%CI:10.03-28.61]、32.27 [95%CI:20.99-49.59],0.93 [95%CI:0.91-0.95]、 0.80 [95%CI:0.76-0.83]、0.91 [95%CI:0.88-0.93].CONCLUSION: Analysis of stool DNA methylation has a reasonable sensitivity and specificity for the detection of colorectal cancer,adenomas and colorectal neoplasia,and may provide a promising and noninvasive screening method for colorectal ancer,adenomas and colorectal neoplasia.Combined detection of multiple methylated genes in fecal DNA is superior to the single gene detection method for CRC,adenomas and colorectal neoplasia screening.