Elevated N6-Methyladenosine RNA Levels in Peripheral Blood Immune Cells: A Novel Predictive Biomarker and Therapeutic Target for Colorectal Cancer

Effective biomarkers for the diagnosis of colorectal cancer (CRC) are essential for improving prognosis. Imbalance in regulation of N6-methyladenosine (mA) RNA has been associated with a variety of cancers. However, whether the mA RNA levels of peripheral blood can serve as a diagnostic biomarker for CRC is still unclear. In this research, we found that the mA RNA levels of peripheral blood immune cells were apparently elevated in the CRC group compared with those in the normal controls (NCs) group. Furthermore, the mA levels arose as CRC progressed and metastasized, while these levels decreased after treatment. The area under the curve (AUC) of the mA levels was 0.946, which was significantly higher than the AUCs for carcinoembryonic antigen (CEA; 0.817), carbohydrate antigen 125 (CA125; 0.732), and carbohydrate antigen 19-9 (CA19-9; 0.771). Moreover, the combination of CEA, CA125, and CA19-9 with mA levels improved the AUC to 0.977. Bioinformatics and qRT-PCR analysis further confirmed that the expression of mA modifying regulator IGF2BP2 was markedly elevated in peripheral blood of CRC patients. Gene set variation analysis (GSVA) implied that monocyte was the most abundant mA-modified immune cell type in CRC patients' peripheral blood. Additionally, mA modifications were negatively related to the immune response of monocytes. In conclusion, our results revealed that mA RNA of peripheral blood immune cells was a prospective non-invasive diagnostic biomarker for CRC patients and might provide a valuable therapeutic target.