Abstract 2654: Immunologic and prognostic correlates of WISP1 in prostate cancer

Abstract

Background: Avoidance of immune destruction and tumor-promoting inflammation are equally important cancer hallmarks. In the context of prostate cancer, inflammatory markers and high levels of immune infiltrates have been associated with shorter biochemical recurrence (BCR)-free survival. WNT1 Inducible Signaling Pathway (WISP1) has been implicated in prostate cancer metastasis and the regulation of inflammation in diverse benign diseases. Thus, the objectives of this study were: 1) to assess the prognostic value of WISP1 in human prostate cancer, and 2) to determine the association of WISP1 to the inflammatory landscape specific to this disease. Methods: A tumor microarray (TMA) was constructed with radical prostatectomy specimens of 285 prostate cancer patients. Multicolor manual immunofluorescence (IF) was performed to simultaneously detect WISP1, CD8 and cytokeratins 8 and 18. WISP1 expression levels were determined by the mean fluorescence intensity (MFI) in stromal, epithelial, cytoplasmic and nuclear (DAPI) areas in each core, and CD8+ cell density was determined for each compartment by dividing cell count by the percentage of the core occupied by the compartment. Finally, the prostate cancer TCGA dataset (n = 548) was used to validate the prognostic value of WISP1 mRNA expression, as well as its association to CD8+ lymphocytes using previously validated gene signatures (Becht et al., 2016). Results: IF analyses of our TMA revealed that high levels of WISP1 in normal adjacent epithelium are significantly associated with shorter BCR-free survival in Kaplan-Meier (log-rank = 4.246, p = 0.039) and univariate Cox regression analyses (hazard ratio = 1.477; p = 0.042), but not in multivariate Cox regression analyses (hazard ratio = 1.381; p = 0.101). Furthermore, a significant correlation was found between WISP1 expression and CD8+ cell density. Gene expression analyses further showed that WISP1-high prostate tumors are associated with a CD8+ lymphocyte gene enrichment profile, and confirmed that patients with WISP1-high prostate tumors have reduced BCR-free survival (Wilcoxon rank, p = 0.003). Conclusions: Overall, our results support a negative prognostic association for WISP1 as well as a proinflammatory role. WISP1 may represent a relevant target for the improvement of prostate cancer immunotherapy. Citation Format: Pierre-Olivier Gaudreau, Sylvie Clairefond, Pierre-Luc Boulay, Pavel Chrobak, Bertrand Allard, Sandra Pommey, Fred Saad, Marian Young, John Stagg. Immunologic and prognostic correlates of WISP1 in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2654.