High stroma-derived WNT5A is an indicator for low-risk prostate cancer

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Prostate cancer (PCa) is a major cause of cancer-related death in men. Tumor-derived protein derived from Wnt5A gene (WNT5A) plays an important role in primary and metastatic PCa. Surrounding stroma cells also produce WNT5A, which may modulate the biology of PCa. Here, we assessed the role of stroma-derived WNT5A (stWNT5A) in primary PCa. A tissue microarray of samples obtained from 400 patients who underwent radical prostatectomy and control samples from 41 patients with benign prostate hyperplasia (BPH) was immunohistochemically assessed for expression of stWNT5A. The cores were scored for staining intensity: 0 (no staining), 1 (weak), 2 (moderate), or 3 (strong) and the stained stromal surface area: 0 (0%), 1 (1-25%), 2 (26-50%), 3 (51-75%), or 4 (76-100%). Gleason Score (GS) and TNM-stage were assessed by stratifying the cohort into high-risk (≥ pT3, pN1, GS ≥ 8) and non-high-risk patients. Ki67 and TUNEL assays were performed to assess proliferation and apoptosis. Expression of stWNT5A in BPH and tumor-free control samples was 1.2-fold higher compared to tumor samples (P < 0.001). Non-high-risk patients had a higher stWNT5A score than high-risk patients (P < 0.05). stWNT5A expression was not correlated with overall and cancer-specific survival. Proliferation (r2 = 0.038, P < 0.001) and apoptosis (r2 = 0.277, P < 0.001) negatively correlated with stWNT5A expression. In summary, we show that expression of stWNT5A is higher in benign tissue and non-high-risk PCa. Stroma-derived Wnt signaling and tumor-derived Wnt may differentially impact on tumor behavior. Future studies are warranted to dissect the Wnt profile in tumor vs. surrounding stroma tissues.

Details

Original languageEnglish
Pages (from-to)1186-1194
Number of pages9
JournalFEBS open bio
Volume11
Issue number4
Publication statusPublished - Apr 2021
Peer-reviewedYes

External IDs

PubMedCentral PMC8016115
Scopus 85102307383
ORCID /0000-0002-8691-8423/work/142236041

Keywords

Sustainable Development Goals

Keywords

  • Aged, Biomarkers, Tumor, Cancer-Associated Fibroblasts, Cell Line, Tumor, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Prostatic Neoplasms/etiology, Stromal Cells/metabolism, Tissue Array Analysis, Wnt-5a Protein/genetics