Abstract: Objective To screen out the candidate fecal microRNAs(miRNAs)that play a crucial role in the occurrence of advanced adenoma and evaluate their clinical value in the screening and diagnosis of advanced adenoma. Methods From June 2022 to December 2023, 110 patients with colorectal cancer treated at the Affiliated Hospital of Chengde Medical University were selected as the colorectal cancer group, 94 patients with advanced adenoma as the advanced adenoma group, and 80 healthy individuals undergoing physical examinations as the control group. Five colorectal cancer patients cancerous and adjacent tissues were sequenced using next-generation sequencing to identify abnormally expressed miRNAs. Quantitative real-time PCR(qRT-PCR)was used to detect the expression of abnormally expressed miRNAs in the faeces of 30 patients in the colorectal cancer group and 20 in the control group to obtain abnormal miRNAs in faeces. The colorectal cancer group, advanced adenoma group, and control group were randomly divided into a training cohort and a validation cohort in a 7∶3 ratio. qRT-PCR was used to detect the expression of abnormal miRNAs in faeces in both cohorts, and the screening and diagnostic efficacy of miR-29a-3p was evaluated using the receiver operating characteristic(ROC)curve. To verify the screening and diagnostic efficacy of miR-29a-3p, 3,039 subjects who underwent colonoscopy during the same period were used as the observation group, with direct colonoscopy and pathological examination when necessary to calculate the detection rate of advanced adenomas. Eighty-one subjects were used as the screening group, with faecal miR-29a-3p detection followed by colonoscopy and pathology if necessary,to calculate the detection rate of advanced adenomas in those with elevated faecal miR-29a-3p. The chi-squared test was used to compare the detection rates of the observation and screening groups. Results Five miRNAs(let-7c-5p,miR-203a-3p,miR-122-5p,miR-29a-3p,miR-92b-3p)were significantly higher in cancer tissues than adjacent tissues.Through the training cohort, it was confirmed that miR-29a-3p was significantly upregulated in feces of the advanced adenoma group(P<0.05), and the area under the ROC curve(AUC)for the diagnosis of advanced adenomas using faecal miR-29a-3p in combination with faecal occult blood test, gender and smoking history was 0.840. Further confirmation by the validation cohort showed that miR-29a-3p was highly expressed in faeces of the advanced adenoma group(P<0.05), and the combination of faecal miR-29a-3p with fecal occult blood test, gender and smoking history could be used for the diagnosis of advanced adenomas(AUC=0.807). The colonoscopy detection rate of advanced adenomas in the screening group using elevated fecal miR-29a-3p as a screening indicator was 39.2%, which was statistically different from the observation group(P<0.05). Conclusion miR-29a-3p is significantly upregulated in feces of advanced adenoma patients, and fecal miR-29a-3p has a high clinical diagnostic value for advanced adenoma.

Key words: Advanced adenomas, Colorectal cancer, Faeces, Diagnosis, Biomarker, microRNA-29a-3p