Published online Jun 6, 2022. doi: 10.12998/wjcc.v10.i16.5165
Peer-review started: October 22, 2021
First decision: December 27, 2021
Revised: December 29, 2021
Accepted: March 15, 2022
Article in press: March 15, 2022
Published online: June 6, 2022
Processing time: 223 Days and 8 Hours
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 nonin
To identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.
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.
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.
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.
Core Tip: This report is the first on the diagnostic usefulness of circulating miR-627-5p and miR-199a-5p in patients with colorectal neoplasms. We identified that serum levels of miR-627-5p and miR-199a-5p were markedly elevated in patients with colorectal neoplasia and appeared to be novel biomarkers for the non-invasive screening of colorectal neoplasia. An integrated model combining miR-199a-5p and miR-627-5p obtained a better discriminative capacity than each miRNA alone. Additionally, miR-627-5p and miR-199a-5p had different expression levels in the serum of cancer patients before and after surgery and in vitro gain-of-function experiments demonstrated that both microRNAs played crucial roles in regulating the progression and invasion of colorectal cancer cells.