m⁶A target microRNAs in serum for cancer detection

Recent studies have revealed the significant dysregulation of m⁶A level in peripheral blood in several cancer types and its value in diagnosis. Nonetheless, a biomarker for accurate screening of multiple cancer types has not been established based on the perspective of m⁶A modification. In this study, we aimed to develop a serum diagnostic signature based on the m⁶A target miRNAs for the mass detection of cancer. A total of 14965 serum samples with 12 cancer types were included. Based on training cohort (n=7299), we developed the m6A-miRNAs signature using a support vector machine algorithm for cancer detection. The m6A-miRNAs signature showed high accuracy, and its area under the curve (AUC) in the training, internal validation and external validation cohort reached 0.979 (95%CI 0.976 - 0.982), 0.976 (95%CI 0.973 - 0.979) and 0.936 (95%CI 0.922 - 0.951), respectively. In the performance of distinguishing cancer types, the m6A-miRNAs signature showed superior sensitivity in each cancer type and presented a satisfactory AUC in identifying lung cancer, gastric cancer and hepatocellular carcinoma. Additionally, the diagnostic performance of m6A-miRNAs was not interfered by the gender, age and benign disease. In short, this study revealed the value of serum circulating m⁶A miRNAs in cancer detection and provided a new direction and strategy for the development of novel biomarkers with high accuracy, low cost and less invasiveness for mass cancer screening, such as RNA modification.