Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer

Abstract

Previous studies from our laboratory identified a number of miRNAs that were aberrantly expressed in colorectal cancer (CRC) tissue. However, their diagnostic and prognostic value in serum has not been fully evaluated. In the present study, we measured the levels of 5 miRNAs (miR-21, 31, 92a, 18a and 106a) in serum samples from 200 CRC patients, 50 advanced adenoma patients, and 80 healthy controls by real-time quantitative polymerase chain reaction (RT-PCR). In our study, the levels of miR-21 and miR-92a in patients with CRC and advanced adenoma were significantly higher than those in healthy controls (all P < 0.05). MiR-21 yielded an area under the ROC curve (AUC) of 0.802 and miR-92a yielded an AUC of 0.786 in discriminating CRCs from the controls. Additionally, miR-21 and miR-92a yielded an AUC of 0.709 and 0.701, respectively, in discriminating advanced adenomas from the controls. Combined receiver-operating characteristics (ROC) analyses, using both miRNAs, revealed an elevated AUC of 0.847 in discriminating CRCs, and an AUC of 0.722 in discriminating advanced adenomas from the controls. In the multivariate Cox proportional hazards analysis, high miR-92a expression in CRC was independently associated with poor survival (P = 0.03; hazard ratio 4.36; 95% confidence interval = 1.64-11.57). In summary, our data indicate that miR-21 and miR-92a serum levels have potential value for early detection of CRC. Furthermore, miR-92a has prognostic value in CRC patients. No significant difference was observed in the levels of miR-18a, 31 and 106a among CRC, advanced adenoma and control samples.

Diagnostic and Prognostic Value of microRNA-21 in Colorectal Cancer: An Original Study and Individual Participant Data Meta-analysis

“…In a study conducted by Toiyama and colleagues (17), in which 43 patients with Japanese advanced adenoma and 53 control subjects were enrolled, miR21 had a relatively high diagnostic performance for advanced adenoma (AUC value of 0.813, sensitivity of 0.811, and a specificity of 0.767). In another study, which included 50 Chinese advanced adenoma patients and 80 healthy controls, miR21 yielded an AUC value of 0.709 for discriminating advanced adenomas from controls (18). However, it should be noted that these two studies were both conducted in East Asia and the sample size was not large; thus, more studies are warranted to clarify this issue.…”

“…Besides, whether the prognostic value of other miRNAs is differed by gender may also need further study. Circulating miR21 was also developed as a noninvasive prognostic biomarker for colorectal cancer, and studies indicated that higher circulating miR21 level might be associated with poor OS for colorectal cancer (17,18).…”

“…Finally, a total of 13 articles were identified as eligible studies (10,(16)(17)(18)(19)(29)(30)(31)(32)(33)(34)(35)(36). With our original study, 14 studies were finally included in the meta-analyses.…”

“…Two studies explored the performance of circulating miR21 levels in the prognosis of colorectal cancer (17,18). The HR of these two studies for colorectal cancer OS was 4.12 (95% CI, 1.10-15.4) and 1.58 (95% CI, 0.77-3.21), respectively.…”

“…Furthermore, it can influence patients survival and response to chemotherapy (10,15,16). Many studies have evaluated the application of miR21 in the diagnosis and prognosis of colorectal cancer; however, the results were contradictive (10,(17)(18)(19). As a consequence, the aim of this study was to comprehensively explore the potential value of miR21 in colorectal cancer diagnosis and prognosis.…”