Genetic variants in the Hippo pathway predict biochemical recurrence after radical prostatectomy for localized prostate cancer
Journal
Scientific Reports
Journal Volume
5
Pages
8556
Date Issued
2015
Author(s)
Abstract
While localized prostate cancer is potentially curative, many patients still show biochemical recurrence (BCR) after curative treatments such as radical prostatectomy (RP). The Hippo pathway has recently been shown to be an evolutionarily conserved regulator of tissue growth, and its perturbation can trigger tumorigenesis. We hypothesize that genetic variants of the Hippo pathway may influence clinical outcomes in localized prostate cancer patients. We genotyped 53 tagging single-nucleotide polymorphisms (SNPs) from seven core Hippo pathway genes in 246 localized prostate cancer patients treated with RP. Kaplan-Meier analysis and Cox proportional hazard models were utilized to identify significant SNPs that correlated with BCR. For replication, five associated SNPs were genotyped in an independent cohort of 212 patients. After adjusting for known clinicopathologic factors, the association between STK3 rs7827435 and BCR (P = 0.018) was replicated in the second stage (P = 0.026; P combined = 0.001). Additional integrated in silico analysis provided evidence that rs7827435 affects STK3 expression, which in turn is significantly correlated with tumor aggressiveness and patient prognosis. In conclusion, genetic variants of the Hippo pathway contribute to the variable outcomes of prostate cancer, and the discovery of these biomarkers provides a molecular approach for prognostic risk assessment.
SDGs
Other Subjects
messenger RNA; protein serine threonine kinase; STK3 protein, human; aged; allele; cancer staging; cohort analysis; follow up; genetics; genotype; human; Kaplan Meier method; male; metabolism; middle aged; mortality; pathology; proportional hazards model; prostate tumor; prostatectomy; quantitative trait locus; signal transduction; single nucleotide polymorphism; tumor recurrence; Aged; Alleles; Cohort Studies; Follow-Up Studies; Genotype; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Polymorphism, Single Nucleotide; Proportional Hazards Models; Prostatectomy; Prostatic Neoplasms; Protein-Serine-Threonine Kinases; Quantitative Trait Loci; RNA, Messenger; Signal Transduction
Publisher
Nature Publishing Group
Type
journal article