Naslov
THE RELATIONSHIP OF B7H3 EXPRESSION TO ANDROGEN AND PROSTATE CANCER OUTCOMES IN A LARGE NATURAL HISTORY COHORT OF MEN UNDERGOING PROSTATECTOMY

Autori
Ashley Ross , Benjamin Benzon , Shuang Zhao , Mandeep Takhar , Michael Haffner , Nicholas ErhoPaula Hurley , Jeffrey J. Tosoian , Mohammed Alshalalfa , Stephanie Glavaris , Brian Simons , Phuoc T. Tran , Elai Davicioni , Jeffrey Karnes , Edward M. Schaeffer , Charles G. Drake , Felix Yi- Chung Feng

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Journal of Clinical Oncology / - , 2016

Skup
Prostate Cancer Foundation

Mjesto i datum
San Francisco (CA), Sjedinjene Američke Države, 07.01.2016. - 09.01.2016

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
prostate cancer, immunotherapy

Sažetak
INTRODUCTION AND OBJECTIVES B7-H3 (CD276), part of the B7 superfamily, has been shown to play an immunomodulatory role, however its regulation, receptor and mechanism of action remain unclear. Protein levels of B7-H3 have been previously shown to relate to prostate cancer outcomes and currently, humanized monoclonal antibodies are being developed for clinical use (MGA271, Macrogenics). Here we use genomic expression data to examine the relationship of B7-H3 to prostate cancer outcomes, and molecular subtypes and explore its relationship to other gene sets and pathways. METHODS Prostatectomy tissue from 905 patients were profiled using the Affymetrix HuEx 1.0 ST microarray. Kruskal-Wallis tests were used to identify significant associations of B7-H3 expression with clinico-pathologic variables, and survival analysis was used to evaluate the prognostic value of B7-H3. Pearson’s correlation analyses were also performed to assess the relationship of B7-H3 expression with molecular subtypes and individual transcripts. Androgen receptor (AR) occupancy of promoter regions was derived in silico from chromosomal immune- precipitation (ChIP) data. RESULTS B7-H3 expression was positively associated with Gleason score (p < 0.01) and tumor stage (p < 0.01). High B7-H3 expression also correlated with the development of metastasis and prostate cancer specific mortality (HR of 3.4 and 2.4 respectively, p < 0.05 for both), but this was not significant on multi-variable analysis. B7-H3 was positively associated with ERG+ disease (n = 670, r = 0.85, p < 0.05) and AR expression (n = 670, r = 0.46, p < 0.001). B7-H3 was found to be one of the most correlated genes with AR (95th percentile) and ChIP analysis revealed androgen dependent AR binding upstream of B7-H3. Gene set enrichment analysis demonstrated a positive correlation with androgen signaling and a negative correlation with the defensins reactome (FDR <0.002). CONCLUSIONS B7-H3 expression correlates with high Gleason grade and advanced prostate cancer stage with higher quartiles of expression portending poor oncologic outcomes in two independent prostatectomy cohorts. B7-H3 expression appears to relate to androgen receptor signaling and modulation of immune pathways.

Izvorni jezik
Engleski

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