Molecular and Clinicopathological Correlates of Wild-Type KRAS Expression in Prostate Cancer

Abstract

Background The clinicopathological significance of KRAS alterations in clinical prostate cancer (PCa) has yet to be comprehensively studied, and the classic KRAS somatic mutations are rare in PCa. Methods The clinico-genomic data of two PCa cohorts were retrieved from the cancer genome databases. KRAS expression-based gene enrichment for cell proliferation, apoptosis, and epithelial-mesenchymal transition /invasion programmes, RAS activation, MAPK and PI3K signalling were sought using gene enrichment analyses, and validated with clinicopathologically relevant tumour biology signatures. Results RAS activation and hallmark tumour biology pathways were enriched in KRAS-high PCa subsets. KRAS expression also demonstrated significant associations with Gleason score and ISUP prognostic grade groups, pathological tumour stage, overall TNM stage, and treatment outcomes, but not with age, pathological node and metastasis statuses. The study further demonstrated that wild-type KRAS expression was deregulated in PCa by a combination of copy number changes, epigenetic/altered transcription factor-expression and microRNA mechanisms. Conclusion The relevance of KRAS expression to clinical PCa biology and therapy outcomes deserves further validation.