Pierre-Olivier Gaudreau1, Sylvie Clairefond2, Caleb A Class3, Pierre-Luc Boulay4, Pavel Chrobak2, Bertrand Allard2, Feryel Azzi5, Sandra Pommey2, Kim-Anh Do3, Fred Saad6, Dominique Trudel7, Marian Young8, John Stagg9. 1. Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. 2. Axe Cancer, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada. 3. T. Boone Pickens Academic Tower, University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Département de pharmacologie et de physiologie, Université de Montréal, Montreal, QC, Canada. 5. Centre de Recherche du Centre Hospitalier Universitaire de Montréal (CRCHUM)/Institut du Cancer de Montréal, Montreal, QC, Canada. 6. Département d'Urologie du Centre Hospitalier Universitaire de Montréal (CHUM) et Institut du Cancer de Montréal / CRCHUM, Montreal, QC, Canada. 7. Centre Hospitalier de l'Université de Montréal (Département de pathologie), Département de pathologie et axe cancer, Université de Montréal (Département de pathologie et de biologie cellulaire) et Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada. 8. NIDCR, National Institutes of Health, Bethesda, MD, USA. 9. Faculté de Pharmacie, Université de Montréal et Institut du Cancer de Montréal / CRCHUM, Axe Cancer, Montreal, QC, Canada.
Abstract
Background: WNT1-Inducible Signaling Pathway Protein 1 (WISP1) is implicated in prostate cancer growth and metastasis and the regulation of inflammation in diverse benign diseases. The objectives of this study were to assess the prognostic value of WISP1, its association to inflammation and its relevance as a biomarker for immune checkpoint blockade (ICB) response. Methods: Publicly available RNA-seq datasets were used to evaluate the prognostic value of WISP1 gene expression and its association with tumor-infiltrating lymphocytes, inflamed tumor microenvironment, and anti-PD-1 ICB response. A tissue microarray (TMA) including 285 radical prostatectomy specimens was used to confirm these associations in prostate cancer. The effect of recombinant WISP1 (rWISP1) on inflammatory cytokines was assessed in vitro. Results: High levels of WISP1 correlated with BCR-free survival in prostate adenocarcinoma and overall survival in primary melanoma, low-grade glioma, and kidney papillary cell carcinoma. Some effects could be accounted for by higher WISP1 expression in advanced disease. High WISP1 expression in prostate adenocarcinoma was correlated with CD8+ cells density. In vitro, rWISP1 increased inflammatory cytokine production. High WISP1 gene expression in RNA-seq datasets was correlated with gene signatures of multiple immune cell types as well as an inflammatory cytokine, immune checkpoint, and epithelial-mesenchymal transition (EMT) gene expression. WISP1 mRNA expression was associated with primary resistance to ICB in datasets showing EMT. Conclusions: Our results support an association between WISP1 expression and advanced disease, EMT and an inflamed tumor microenvironment in multiple solid tumors. The consequences of WISP1 expression on cancer immunotherapy remains to be addressed.
Background: WNT1-Inducible Signaling Pathway Protein 1 (WISP1) is implicated in prostate cancer growth and metastasis and the regulation of inflammation in diverse benign diseases. The objectives of this study were to assess the prognostic value of WISP1, its association to inflammation and its relevance as a biomarker for immune checkpoint blockade (ICB) response. Methods: Publicly available RNA-seq datasets were used to evaluate the prognostic value of WISP1 gene expression and its association with tumor-infiltrating lymphocytes, inflamed tumor microenvironment, and anti-PD-1 ICB response. A tissue microarray (TMA) including 285 radical prostatectomy specimens was used to confirm these associations in prostate cancer. The effect of recombinant WISP1 (rWISP1) on inflammatory cytokines was assessed in vitro. Results: High levels of WISP1 correlated with BCR-free survival in prostate adenocarcinoma and overall survival in primary melanoma, low-grade glioma, and kidney papillary cell carcinoma. Some effects could be accounted for by higher WISP1 expression in advanced disease. High WISP1 expression in prostate adenocarcinoma was correlated with CD8+ cells density. In vitro, rWISP1 increased inflammatory cytokine production. High WISP1 gene expression in RNA-seq datasets was correlated with gene signatures of multiple immune cell types as well as an inflammatory cytokine, immune checkpoint, and epithelial-mesenchymal transition (EMT) gene expression. WISP1 mRNA expression was associated with primary resistance to ICB in datasets showing EMT. Conclusions: Our results support an association between WISP1 expression and advanced disease, EMT and an inflamed tumor microenvironment in multiple solid tumors. The consequences of WISP1 expression on cancer immunotherapy remains to be addressed.
Authors: Barry S Taylor; Nikolaus Schultz; Haley Hieronymus; Anuradha Gopalan; Yonghong Xiao; Brett S Carver; Vivek K Arora; Poorvi Kaushik; Ethan Cerami; Boris Reva; Yevgeniy Antipin; Nicholas Mitsiades; Thomas Landers; Igor Dolgalev; John E Major; Manda Wilson; Nicholas D Socci; Alex E Lash; Adriana Heguy; James A Eastham; Howard I Scher; Victor E Reuter; Peter T Scardino; Chris Sander; Charles L Sawyers; William L Gerald Journal: Cancer Cell Date: 2010-06-24 Impact factor: 31.743
Authors: Aravind Subramanian; Pablo Tamayo; Vamsi K Mootha; Sayan Mukherjee; Benjamin L Ebert; Michael A Gillette; Amanda Paulovich; Scott L Pomeroy; Todd R Golub; Eric S Lander; Jill P Mesirov Journal: Proc Natl Acad Sci U S A Date: 2005-09-30 Impact factor: 11.205
Authors: Kaliyamurthi Venkatachalam; Balachandar Venkatesan; Anthony J Valente; Peter C Melby; Sailesh Nandish; Jane E B Reusch; Robert A Clark; Bysani Chandrasekar Journal: J Biol Chem Date: 2009-04-01 Impact factor: 5.157