Predictive value of m6A regulators in prognosis and immunotherapy response of clear cell renal cell carcinoma: a bioinformatics and radiomics analysis

Aim: This study aimed to develop an m6A-related gene signature for predicting the prognosis of clear cell renal cell carcinoma (ccRCC) patients and explore its value in predicting the immunotherapy response. Methods: In total, 530 ccRCC patients with gene expression data in the TCGA cohort were included and classified into the training (n = 371) and validation (n = 159) sets. Differential expression analyses of 23 m6A regulators between survivors and non-survivors were performed. Subsequently, an m6A-related gene signature was developed via LASSO Cox regression. All patients were categorized into two groups of m6A subtypes, i.e., low or high m6A score group. The Kaplan-Meier survival curves and Tumor Immune Dysfunction and Exclusion (TIDE) scores of the two m6A subtype groups were compared to measure the gene signature’s predictive value in prognosis and potential immunotherapy response, respectively. Results : Eighteen m6A regulators were significantly differentially expressed between the survivors and non-survivors, and were also related to overall survival (OS). A gene signature containing five selected m6A methylation regulators (KIAA1429 , METTL14 , IGF2BP2 , IGF2BP3 , and SRSF2 ) was developed and showed favorable discrimination in the training (C-index 0.708) and validation (C-index 0.689) sets. Patients with low m6A scores had significantly better OS and lower TIDE scores than those with high m6A scores. Moreover, a robust MRI-based radiomic signature was developed to noninvasively predict the m6A subtype for each patient. Conclusion : We demonstrated the prognostic value of five m6A regulators and constructed a gene signature for prognosis and immunotherapy response prediction among ccRCC patients. In addition, a radiomic signature was developed for noninvasive prediction of the m6A subtype. These findings may promote precision medicine and provide novel insights into the regulation of tumor immune microenvironment.