Combined Plasma MicroRNA and Fecal Occult Blood Tests in Early Detection of Colorectal Cancer.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies and a major cause of cancer-related death worldwide. Fecal occult blood tests (FOBT) are non-invasive colorectal cancer screening tests. In recent years plasma microRNAs (miRNAs) have shown great potential in early non-invasive cancer detection. METHODS: FOBT (immunochemical) and a panel of 12 plasma miRNAs were tested in two independent groups 57 CRC patients and 125 neoplasm free controls, in addition to 58 advanced adenoma patients and 67 neoplasm free controls. miRNA levels were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Plasma levels of 7 miRNAs (miR-18a, miR-20a, miR-21, miR-92a, miR-133a, miR-143, miR-145) differed significantly between CRC patients and neoplasm free controls. miRNA plasma levels did not differ between advanced adenoma patients and controls. For 7 dysregulated miRNAs in CRC patients, AUCs ranged from 0.585 to 0.632 for CRC detection, in comparison to an AUC of 0.857 for iFOBT. The combination of miR-133a and iFOBT achieved a higher AUC (0.894) than iFOBT alone. At 97.8% specificity, miRNAs showed much lower sensitivities than iFOBT, but the miRNA panel and iFOBT in combination detected CRC with a higher sensitivity than iFOBT alone. CONCLUSIONS: The diagnostic performance of miRNAs was poorer than iFOBT. Nevertheless, plasma miRNA profiles offer an innovative non-invasive approach for early CRC detection. The potential advantage of combining plasma miRNA profiles with iFOBT needs to be further studied in a larger cohort of patients.