Detection of miR-34a and miR-34b/c in stool sample as potential screening biomarkers for noninvasive diagnosis of colorectal cancer

Abstract

Explore potential screening biomarkers for noninvasive diagnosis of colorectal cancer (CRC) by testing methylation of the miR-34a and miR-34b/c promoter in CRC patients' tissue and stool samples. Methylation-specific PCR analyses were performed on sample DNAs: 82 pairs of normal/cancer samples, 82 CRC patients' stool samples, 40 healthy volunteer stool samples, and 20 healthy volunteer blood samples were recruited. miR-34a has been found methylated in 65 of 82 (79.3%) the CRC tissue samples, but only 36 of 82 (43.9%) in corresponding normal samples. And when testing miR-34a in stool, 63 of 82 (76.8 %) CRC stool samples were observed methylated, and 2 of 40 (5%) healthy samples were observed methylated. The methylation for miR-34b/c has been found in 80 of 82 (97.5%) CRC tissue samples, 49 of 82 (59.8%) corresponding CRC normal samples, and 74 of 79 (93.6%) CRC stool samples. Yet we did not detect any methylation from healthy volunteers stool samples or healthy adult blood samples. Results indicated 76.8 % sensitivity and 93.6% specificity of the miR-34a methylation test for detecting CRC using stool samples. Meanwhile, the sensitivity and specificity of miR-34b/c were 95 and 100%, respectively. Moreover, our results revealed that abnormal DNA methylation of miR-34a was correlated with lymph metastasis (P = 0.010). Abnormal methylation of miR-34a and miR-34b/c genes might be regarded as potential biomarkers for noninvasive screening and diagnosis of colorectal cancer.