N 6 -methyladenosine levels in peripheral blood RNA: a potential diagnostic biomarker for colorectal cancer.

BACKGROUND: N6 -methyladenosine (m6 A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m6 A levels in CRC.

METHODS: We collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m6 A levels and the expression of m6 A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model.

RESULTS: PB RNA m6 A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m6 A levels (0.886) in the CRC was significantly larger compared with carbohydrate antigen 199 (CA199; 0.666) and carcinoembryonic antigen (CEA; 0.834). The combination of CEA and CA199 with PB RNA m6 A led to an increase in the AUC (0.935). Compared with HCs, the expression of FTO and ALKBH5 was decreased in the CRC. After coculturing with CRC cells, the PBMCs RNA m6 A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m6 A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased.

CONCLUSIONS: PB RNA m6 A levels are a potential diagnostic biomarker for patients with CRC.