Contribuição do sequenciamento genético de 20 genes na análise prognóstica e predição de mortalidade em pacientes com câncer de próstata localizado

Abstract

Prostate cancer is a genetic, phenotypic, and clinically heterogeneous disease. Some PCs are hormone-sensitive, indolent, and localized, while others behave like an aggressive and metastatic disease. Early differentiation between these groups is essential for the therapeutic planning of PC. Part of this differentiation seems to be associated with genetic susceptibility. Genomic association studies have identified polymorphisms in several genes that are significantly associated with susceptibility to prostate cancer It is necessary to develop a more comprehensive stratification, based on molecular biology, that allows identifying genetic characteristics that have prognostic importance in PC, allowing more accurate decision-making in different clinical scenarios. With the advancement of molecular biology and new sequencing technologies, genetic research involving patients with CP was no longer focusing on a point mutation or a single gene and began to map large regions of the genome, in the same analysis. There is growing interest in investigating the potential use of genetic polymorphisms as diagnostic and prognostic biomarkers for CP. To identify and correlate genomic variants as possible predictors of prostate cancer prognosis. Retrospective longitudinal observational cohort study that, based on a review of the medical records of 64 patients who underwent prostatectomy between 2016 and 2018 and who had blood and tumor material previously submitted to next-generation genetic sequencing (SGN) for identification of somatic and germline mutations in 20 genes already recognized and of interest in the pathology of PC: AR; KLF6; PTEN; ZBTB16; CDKN1B; BRCA2; CDH1; BRCA1; SPOP; TP53; TMPRSS2; CHEK2; PIK3CA; COX6C; MYC; NDRG1; AGO2; PTK2; NKX3-1; PAG-1. Patients will be divided into groups according to the clinical outcome (disease-specific death X non-death). The present study is important as it corroborates the role of SNG in the prognostic analysis of PC, correlating specific genetic variants with mortality and biochemical recurrence, showing a possible different genetic signature in Brazilians when pointing to genes less studied in PC such as PAG1 and CDH