Abstract 4892: MicroRNA signature and telomere genes in kidney cancer survival

Abstract Introduction: Kidney cancer ranks among the top 10 most prevalent cancers in the United States, clear cell renal cell carcinoma (ccRCC) has the worst disease specific survival histology. MicroRNAs (miRNAs) have emerged as potential prognostic indicators in various cancers, including kidney cancers. Telomerase, a biomarker associated with uncontrolled cancer cell growth, plays a crucial role in the human kidney cortex's telomere shortening over time. However, the link between miRNAs and telomeres in kidney cancer survival remains underexplored. Our study aims to uncover a miRNA signature capable of predicting 5-year survival in ccRCC patients and to investigate the biological relevance of this signature, particularly its shared pathway enrichment mechanisms with telomere genes. Methods: We extracted miRNA expression profiles from The Cancer Genome Atlas database, comprising 166 patients with ccRCC. To identify a robust miRNA signature predicting 5-year survival in ccRCC, we established an Evolutionary Kidney Survival Estimator (EKSE) using an optimal feature selection algorithm and support vector regression. Additionally, we conducted bioinformatics analyses to uncover common biological pathways between miRNAs and telomere genes using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) categories, encompassing biological processes, molecular functions, and cellular components. Results: EKSE identified a robust signature consisting of 37 miRNAs, achieving a mean correlation coefficient and mean absolute error of 0.82±0.01 and 0.65±0.18, respectively between actual and estimated survival times. The top 10 ranked miRNAs in the signature, including hsa-miR-26a-1-3p, hsa-miR-28-5p, hsa-miR-3913-5p, hsa-miR-3170, hsa-miR-148a-5p, hsa-miR-671-3p, hsa-miR-224-3p, hsa-miR-10a-5p, hsa-miR-29b-1-5p, and hsa-miR-106b-5p, also showed promise in diagnosing ccRCC with AUC values ranging from 0.56 to 0.91. Furthermore, bioinformatics analysis revealed that the miRNA signature targeted well known telomere-associated genes such as TERT, DKC1, CTC1, and RTEL1. Notably, miRNA signature and telomere genes shared several common pathways, including cellular senescence (hsa04218) and proteoglycans in cancer (hsa05205). They also had overlapping GO-Molecular functions, such as DNA-binding transcription factor activity (GO:0003700), histone deacetylase binding (GO:0042826), and promoter-specific chromatin binding (GO:1990841). Conclusions: Our findings suggest an association between microRNAs and telomere genes, potentially playing significant roles in the survival of patients with ccRCC. The identified miRNA signature robustly predicts 5-year survival in ccRCC. The shared biological pathways between these miRNAs and telomere genes offer new insights into the mechanisms driving ccRCC, signaling potential for therapeutic targets and improved prognostic markers in kidney cancer. Citation Format: Srinivasulu Yerukala Sathipati, Rohit Sharma, Scott Hebbring. MicroRNA signature and telomere genes in kidney cancer survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4892.