WISP1 is associated to advanced disease, EMT and an inflamed tumor microenvironment in multiple solid tumors

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.

WISP1 Predicts Clinical Prognosis and Is Associated With Tumor Purity, Immunocyte Infiltration, and Macrophage M2 Polarization in Pan-Cancer

“…Although the expression and function of WISP1 implicates it as an oncogene, it may play diverse roles in different types of cancer. In prostate adenocarcinoma, WISP1 expression is associated with shorter biochemical RFS (Gaudreau et al, 2019). In melanoma, the presence of WISP1 in the tumor microenvironment stimulates invasion and metastasis by promoting an epithelial-mesenchymal transition-like process (Deng et al, 2019).…”

RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1

“…WISP1 was originally discovered as a molecule acting downstream of WNT1 and β-catenin to mediate β-catenin-induced tumorigenesis (Pennica et al, 1998). Previous studies revealed that WISP1 was highly expressed in a variety of cancers, including prostate cancer (Ono et al, 2013;Gaudreau et al, 2019), breast cancer (Chiang et al, 2015), lung cancer , and melanoma (Deng et al, 2019), suggesting that WISP1 may promote oncogenesis. Although discrepancies exist in CRC studies, as for instance Khor et al (2006) demonstrated WISP1 enrichment in welldifferentiated colorectal tumors while Davies et al (2010) showed association of higher WISP1 expression with poorly differentiated tumors, there is strong evidence from both studies that WISP1 plays a role in promoting CRC progression and aggressiveness.…”

The Effects of WISP1 Polymorphisms on the Prognosis of Lung Cancer Patients with Platinum-Based Chemotherapy

“… 9 High levels of WISP1 correlated with survival in prostate adenocarcinoma and overall survival in primary melanoma, low-grade glioma, and kidney papillary cell carcinoma. 29 WISP1 could regulate complex biological process during disease by effecting proliferation, cell survival, and cell differentiation, development and disease. 10 , 16 , 30 , 31 It had been pointed out that WISP1 protects lung carcinoma cells from intrinsic p53-dependent, but not extrinsic Fas ligand-activated.…”