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. 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. 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. PB RNA m6A levels are a potential diagnostic biomarker for patients with CRC.

中文翻译：

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外周血 RNA 中的 N6-甲基腺苷水平：结直肠癌的潜在诊断生物标志物

N6-甲基腺苷 (m6A) 在多种癌症中失调，包括结直肠癌 (CRC)。在此，我们评估外周血 (PB) m6A 水平在 CRC 中的诊断潜力。我们收集健康对照（HC）和CRC患者的PB，分析PB RNA m6A水平以及m6A相关去甲基化酶基因FTO和ALKBH5的表达，将CRC细胞与PB单核细胞（PBMC）共培养，并构建MC38癌症模型。CRC 中的 PB RNA m6A 水平高于 HC 中的水平。CRC 中 m6A 水平 (0.886) 的曲线下面积 (AUC) 明显大于糖抗原 199 (CA199; 0.666) 和癌胚抗原 (CEA; 0.834)。CEA 和 CA199 与 PB RNA m6A 的组合导致 AUC 增加 (0.935)。与HC相比，CRC中FTO和ALKBH5的表达降低。与CRC细胞共培养后，PBMCs RNA m6A显着增加，而FTO和ALKBH5的表达减少。此外，MC38癌症模型PB中的m6A RNA水平上调，而FTO和ALKBH5的表达下降。PB RNA m6A 水平是 CRC 患者的潜在诊断生物标志物。