Circulating miR-627-5p and miR-199a-5p are promising diagnostic biomarkers of colorectal neoplasia

摘要

BACKGROUND Early detection of colorectal neoplasms,including colorectal cancers(CRCs)and advanced colorectal adenomas(AAs),is crucial to improve patient survival.Circulating microRNAs(miRNAs)in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers,but their potential for screening colorectal neoplasms remains ambiguous.AIM To identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.METHODS The study was divided into three phases:(1)Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods;(2)an independent set of serum samples from 60 CRC patients,60 AA patients and 30 healthy controls(HCs)was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs,and their diagnostic power was detected by receiver operating characteristic(ROC)analysis;and(3)the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues.RESULTS Based on bioinformatics analysis,miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study.Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs.The diagnostic power of miR-672-5p yielded an area under the curve(AUC)value of 0.90,and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs.A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA.Additionally,the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines,suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived.Furthermore,in vitro experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells.CONCLUSION Serum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.