Identification of New mA Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients.

N6-methyladenosine (mA) is the product of the most prevalent mRNA modification in eukaryotic cells. Accumulating evidence shows that tumor microenvironment (TME) plays a pivotal role in tumor development. However, the underlying relationship between mA modification and the TME of a papillary renal cell carcinoma (PRCC) is still unclear. To investigate the relationship between mA modification and prognosis and immunotherapeutic efficacy for PRCC, we looked for distinct mA modification patterns based on 23 mA-related genes. Next, the correlation between mA modification patterns and TME-related characteristics was investigated. Then, the intersected differentially expressed genes were selected and the scoring system, denoted as mA score, was established to evaluate mA modification, prognosis, and immunotherapeutic efficacy. In this study, three distinct mA expression clusters were identified. Based on the results of immune cell infiltration analysis and functional analysis, carcinogenic pathways, TME-related immune cells, and pathways were identified as well. More importantly, the established mA score showed good value in predicting clinical outcomes according to results using external cohorts. Specifically, PRCC patients with low mA score value showed better survival, immunotherapeutic response, and higher tumor mutation burden. Furthermore, immunohistochemistry using PRCC clinical samples from our medical center was carried out and verified our results. In conclusion, this study highlights the underlying correlation between mA modification and the immune landscape and, hence, enhances our understanding of the TME and improved the therapeutic outlook for PRCC patients.