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HOXA10 expression profiling in prostate cancer
Author(s) -
Hatanaka Yuji,
de Velasco Marco A.,
Oki Takashi,
Shimizu Nobutaka,
Nozawa Masahiro,
Yoshimura Kazuhiro,
Yoshikawa Kazuhiro,
Nishio Kazuto,
Uemura Hirotsugu
Publication year - 2019
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23761
Subject(s) - biochemical recurrence , prostate cancer , immunohistochemistry , breakpoint cluster region , gene expression profiling , biology , hox gene , gene expression , prostate , cancer research , prostatectomy , pathology , gene , cancer , medicine , genetics , immunology
Background HOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10 , a pleiotropic gene that is critical for normal prostate development. In this study we characterized HOXA10 expression in human and mouse PCa to gain insights into its clinical significance. Methods A meta‐analysis of HOXA10 mRNA expression was carried out across several publicly available data sets. Expression of HOXA10 protein expression was assessed by immunohistochemistry (IHC) using human radical prostatectomy (RP) cases. We correlated HOXA10 expression to clinicopathological features and investigated its relationship to biochemical recurrence (BCR) after RP by the Kaplan‐Meier method. HOXA10 mRNA and IHC protein expression was also examined in a mouse model of Pten ‐null PCa. Results A meta‐analysis of HOXA10 gene expression indicated dysregulated expression of HOXA10 in human PCa. IHC profiling of HOXA10 revealed inverse correlations between HOXA10 expression and Gleason pattern, Gleason score, and pathological stage ( P < 0.01). Patients with low expression profiles of HOXA10 were associated with a higher risk of BCR, (OR, 3.54; 95%CI, 1.21‐16.14; P = 0.049) whereas patients with high HOXA10 expression experienced longer times to BCR ( P = 0.045). However, HOXA10 was not an independent predictor of BCR (OR, 1.52; 95%CI, 0.42‐5.54; P = 0.52). Evaluation of expression patterns of HOXA10 in mouse prostate tumors mimicked that of humans. Conclusions Our findings show that HOXA10 expression is inversely associated with tumor differentiation and high HOXA10 expression is associated with improved BCR‐free survival. This study provides human and mouse evidence to suggest tumor suppressive roles for HOXA10 in the context of prostate cancer.