Panels of mRNAs and miRNAs for decoding molecular mechanisms of Renal Cell Carcinoma (RCC) subtypes utilizing Artificial Intelligence approaches

Abstract

Abstract Renal Cell Carcinoma (RCC) encompasses three histological subtypes, including clear cell RCC (KIRC), papillary RCC (KIRP), and chromophobe RCC (KICH) each of which has different clinical courses, genetic/epigenetic drivers, and therapeutic responses. This study aimed to identify the significant mRNAs and microRNA panels involved in the pathogenesis of RCC subtypes. The mRNA and microRNA transcripts profile were obtained from The Cancer Genome Atlas (TCGA), which were included 611 ccRCC patients, 321 pRCC patients, and 89 chRCC patients for mRNA data and 616 patients in the ccRCC subtype, 326 patients in the pRCC subtype, and 91 patients in the chRCC for miRNA data, respectively. To identify mRNAs and miRNAs, feature selection based on filter and graph algorithms was applied. Then, a deep model was used to classify the subtypes of the RCC. Finally, an association rule mining algorithm was used to disclose features with significant roles to trigger molecular mechanisms to cause RCC subtypes. Panels of 77 mRNAs and 73 miRNAs could discriminate the KIRC, KIRP, and KICH subtypes from each other with 92% (F1-score ≥ 0.9, AUC ≥ 0.89) and 95% accuracy (F1-score ≥ 0.93, AUC ≥ 0.95), respectively. The Association Rule Mining analysis could identify miR-28 (repeat count = 2642) and CSN7A (repeat count = 5794) along with the miR-125a (repeat count = 2591) and NMD3 (repeat count = 2306) with the highest repeat counts, in the KIRC and KIRP rules, respectively. This study found new panels of mRNAs and miRNAs to distinguish among RCC subtypes, which were able to provide new insights into the underlying responsible mechanisms for the initiation and progression of KIRC and KIRP. The proposed mRNA and miRNA panels have a high potential to be as biomarkers of RCC subtypes and should be examined in future clinical studies.