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

Abstract

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.

Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance

“…There is little literature evidence to link the studied miRNAs to SB. Some of them have been connected to neoplastic disease development (miR-1253, miR-1290, miR-194-5p, miR-4536-5p, miR-548ar-5p, miR-590-5p, miR-627-5p, miR-320e, miR-23a-3p, miR-612, miR-23a-3p, miR-30d-5p, and miR-122-5p) [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. The role of let-7b-5p in neuronal development and neuroinflammation has been demonstrated [ 25 ].…”

MicroRNA Biomarkers as Promising Tools for Early Colorectal Cancer Screening—A Comprehensive Review

“…Moreover, in blood samples, several other microRNAs have shown promising results, with high sensitivity values ranging from 80 to 90%. These microRNAs include microRNA-144-3p, -199-3p, -423-5p, -320-3p, -940, -627-5p, -592, and -760, which have been analyzed in studies encompassing more than 100 patients [ 70 , 96 , 98 , 113 , 114 ]. Regarding fecal specimens, microRNA-451a has displayed high sensitivity, specificity, and AUC values of 88.00%, 100.00%, and 0.971, respectively [ 44 ].…”

“…MicroRNAs offer distinct advantages in the early detection of CRC due to their involvement in several signaling pathways [ 71 ]. A plethora of microRNAs, namely, microRNA-21-5p, microRNA-146a, microRNA-135b-5p, microRNA-29a-3p, microRNA-1290, microRNA-592, microRNA-601, microRNA-760, microRNA-130a-3p, microRNA-627-5p, microRNA-199a-5p, microRNA-421, microRNA-130b-3p, microRNA-335-3p, microRNA-34a-5p, and microRNA-27a-3p, have been exhaustively studied for their potential in early diagnosis, focusing on their ability to detect premalignant lesions [ 20 , 45 , 57 , 73 , 82 , 113 , 115 , 116 ].…”

“…Remarkably, the specificity of these microRNAs was comparable to the FIT test [ 20 ]. Additionally, microRNA-199a-5p displayed a sensitivity of 90.00% for advanced adenoma detection in serum samples, positioning it as one of the most promising biomarkers for detecting premalignant lesions [ 113 ].…”