title: Genetic variants in the Hippo pathway predict biochemical recurrence after radical prostatectomy for localized prostate cancer.
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; Pcombined = 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.
authors.affiliation: Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: 1] Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan [2] Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shu-Pin
authors.initials: SP
authors.lastname: Huang
authors.affiliation: 1] Department of Urology, E-Da Hospital, Kaohsiung, Taiwan [2] School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Lin
authors.affiliation: 1] Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan [2] Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan [3] Department of Pharmacy, Tajen University, Pingtung, Taiwan.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Yu
authors.affiliation: Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan.
authors.forename: Ta-Yuan
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Shin-Hun
authors.initials: SH
authors.lastname: Juang
authors.affiliation: 1] Department of Pharmacy, China Medical University, Taichung, Taiwan [2] Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan [3] Department of Nursing, Asia University, Taichung, Taiwan.
authors.forename: Bo-Ying
authors.initials: BY
authors.lastname: Bao
mesh_terms: D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000378:metabolism; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction / Q000235:genetics*; D000099317:Hippo Kinases
chemical_list: D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000090742:Serine-Threonine Kinase 3; C097835:STK3 protein, human; D000099317:Hippo Kinases