Aim:The purpose of our study is to systematically assess the expression of miRNAs in cancer tissue and matched plasma samples and to evaluate their usefulness as non-invasive diagnostic biomarkers for the detection of CRC.
Methods:he study was divided into two phases: firstly, qRT-PCR based TaqMan Low Density MiRNA Arrays (TLDAs) was used to screen the differentially expressed miRNAs in 6 plasma samples of CRC patients and 6 healthy controls. Secondly, marker validation by stem-loop reverse transcription real-time PCR using an independent set of paired cancer tissues (n=88) and matched plasma samples (CRC, n=88; control, n=40). Correlation analysis was determined by Pearson’s test. Receiver operating characteristic curve analyses were applied to obtain diagnostic utility of the differentially expressed miRNAs. Target gene prediction and signal pathway analyses were used to predict the function of miRNAs.
Results:In the screening phase, 42 miRNAs identified to be differentially expressed from Taqman MicroRNA Array. Five of them (miR-375, miR-150, miR-206, miR-125b and miR-126*) were chosen to be validated in plasma and tissue samples. The results indicated that for plasma sample, the expression of miR-375(p<0.0001) and miR-206(p=0.0002) were dysregulated and could discriminate CRC patients from healthy controls. For tissue samples, miR-375(p<0.0001), miR-150(p<0.0001), miR-125b (p=0.0065) and miR-126*(p=0.0009) were down-regulated in CRC patients. Three of them (miR-375, miR-150 and miR-125b) were useful biomarkers for differentiating cancer tissue from adjacent normal mucosa. The level of miR-375 was significantly down-regulated and positively correlated in both tissue and plasma samples(r=0.4663,p=0.0007).
Conclusions:Our results indicate that the down-regulation of miR-375 in plasma and tissue is matched in CRC. Therefore, plasma miR-375 holds a great promise to be an alternative tissue biomarker for CRC detection.