N6-methyladenosine levels in peripheral blood RNA: a potential diagnostic biomarker for colorectal cancer.

Background: N⁶-methyladenosine (m⁶A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m⁶A levels in CRC. Methods: We collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m⁶A levels and the expression of m⁶A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model. Results: PB RNA m⁶A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m⁶A 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 m⁶A 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 m⁶A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m⁶A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased. Conclusions: PB RNA m⁶A levels are a potential diagnostic biomarker for patients with CRC. [ABSTRACT FROM AUTHOR]