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Expression screening of cancer/testis genes in prostate cancer identifies nr6a1 as a novel marker of disease progression and aggressiveness
Author(s) -
Mathieu Romain,
Evrard Bertrand,
Fromont Gaëlle,
RiouxLeclercq Nathalie,
Godet Julie,
Cathelineau Xavier,
Guillé François,
Primig Michael,
Chalmel Frédéric
Publication year - 2013
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.22659
Subject(s) - prostate cancer , cancer , prostate , prostate disease , disease , medicine , gene , cancer research , oncology , pathology , biology , genetics
Abstract BACKGROUND Cancer/Testis (CT) genes are expressed in male gonads, repressed in most healthy somatic tissues and de‐repressed in various somatic malignancies including prostate cancers (PCa). Because of their specific expression signature and their associations with tumor aggressiveness and poor outcomes, CT genes are considered to be useful biomarkers and they are also targets for the development of new anti‐cancer immunotherapies. The aim of this study was to identify novel CT genes associated with hormone‐sensitive prostate cancer (HSPC), and castration‐resistant prostate cancer (CRPC). METHODS To identify novel CT genes we screened genes for which transcripts were detected by RNA profiling specifically in normal testis and in either HSPC or CRPC as compared to normal prostate and 44 other healthy tissues using GeneChips. The expression and clinicopathological significance of a promising candidate—NR6A1—was examined in HSPC, CRPC, and metastatic site samples using tissue microarrays. RESULTS We report the identification of 98 genes detected in CRPC, HSPC and testicular samples but not in the normal controls. Among them, cellular levels of NR6A1 were found to be higher in HSPC compared to normal prostate and further increased in metastatic lesions and CRPC. Furthermore, increased NR6A1 immunoreactivity was significantly associated with a high Gleason score, advanced pT stage and cancer cell proliferation. CONCLUSIONS Our results show that cellular levels of NR6A1 are correlated with disease progression in PCa. We suggest that this essential orphan nuclear receptor is a potential therapeutic target as well as a biomarker of PCa aggressiveness. Prostate 73: 1103–1114, 2013. © 2013 Wiley Periodicals, Inc.