Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity
作者机构:Center for Pathological Diagnosis and ResearchThe Affiliated Hospital of Guangdong Medical UniversityZhanjiang 524001China Department of UrologyThe University of Kansas Medical CenterKansas CityKS 66160USA
出 版 物:《Asian Journal of Andrology》 (亚洲男性学杂志(英文版))
年 卷 期:2023年第25卷第2期
页 面:198-207页
核心收录:
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:Department of Defense Prostate Cancer Research Program [PC190026]
主 题:cell cycle regulation disease progression mitogen-activated protein kinase-8-interacting protein 2 patient survival prostate cancer
摘 要:Mitogen-activated protein kinase-8-interacting protein 2(MAPK8IP2)is a scaffold protein that modulates MAPK signal *** MAPK pathways were heavily implicated in prostate cancer progression,the regulation of MAPK8IP2 expression in prostate cancer is not yet *** assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival ***8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas(TCGA)RNA-sequence project and complementary DNA(cDNA)*** Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free ***8IP2 protein expression was evaluated using the immunohistochemistry *** quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP *** primary prostate cancer tissues,MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic *** MAPK8IP2 expression was strongly correlated with late tumor stages,lymph node invasion,residual tumors after surgery,higher Gleason scores,and preoperational serum prostate-specific antigen(PSA)***8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free *** castration-resistant prostate cancers,MAPK8IP2 expression strongly correlated with androgen receptor(AR)signaling *** cell culture-based experiments,MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer ***,MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 *** results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate *** potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.