MicroRNA-21 and microRNA-146a identification in stool and its clinical significance in colorectal neoplasms

Colorectal carcinoma (CRC) is one of the deadliest killers worldwide and its processes of genesis include a sequence of molecular pathway from adenoma to cancer. Previous study showed that microRNAs played an important role in carcinogenesis. In this study, the different expressions of microRNA-21 (miRNA-21) and microRNA-146a (miRNA-146a) were investigated by quantitate real-time polymerase chain reaction (qRT-PCR) from the tissues of colorectal carcinoma (CRC), colorectal adenoma (CRA) and healthy controls as well as their matched stool samples. The relationship between the expression levels of miRNAs and clinicopathological features were analyzed. Then, the diagnostic values of stool-specific miRNAs for colorectal neoplasms were evaluated. As a result, the expression levels of miRNA-21 were confirmed to be significantly higher in stool and tissue samples of CRC and CRA patients than in healthy controls (P<0.01). The expression of miRNA-21 in CRCs was notably higher than in CRAs (P<0.05). High miRNA-21 expression in CRC patients was strongly associated with advanced TNM stage and lymph node metastasis. The expression level of miRNA-21 in CRA patients was correlated to histological types (P<0.05). There was a statistically positive correlation between miRNA-21 expression in CRC stools and matched tissues samples. Compared with healthy control subjects, the expression of miRNA-146a in CRC patients were decreased (P<0.01). No statistically significant differences were observed in miRNA-146a expression between CRA patients and healthy controls (P>0.05). The expression of miRNA-146a in CRCs was reduced compared with CRAs (P<0.01). Furthermore, the reduced expression of miRNA-146a in CRC patients was correlated with differentiation and TNM staging. Nevertheless, no significant correlation was found between miRNA-146a and clinicopathological features including age, gender, adenoma location, adenoma size, histology and CEA in CRA patients (P>0.05). MiRNA-21, miRNA-146a and combined expression levels in stool robustly distinguished (AUC = 0.877, 0.794, 0.878) CRC and (AUC = 0.769, 0.698, 0.761) CRA patients from controls. And they yielded AUC of 0.699, 0.815 and 0.729 in discriminating CRC patients from CRA patients. We conclude miRNA-21 and miRNA-146a in stool samples have potential values for early detection of colorectal cancer.