High Stromal SFRP2 Expression in Urothelial Carcinoma Confers an Unfavorable Prognosis

Frontiers in Oncology

Chien-Feng Li⁴  Li-Ching Wu⁵  Chung-Hsi Hsing⁷  Hong-Yue Lai⁸  Hsin-Hwa Tsai⁸  Steven K. Huang⁹  Yu-Hsuan Kuo^1,10  Chien-Liang Liu^1,11  Wen-Hsin Tseng^1,12  Chia-Chun Chiu^1,13 

[1] 0Department of Clinical Pathology, Chi Mei Medical Center, Tainan, Taiwan;1National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan;2Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan;3Department of Pathology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;Center for Precision Medicine, Chi Mei Medical Center, Tainan, Taiwan;Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan;Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan;Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan;Department of Medical Science Industries, College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan;Division of Hematology and Oncology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan;Division of Uro-Oncology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan;Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan;Genetics Generation Advancement Corp., Taipei, Taiwan;

关键词: urothelial carcinoma;    bladder cancer;    upper urinary tract cancer;    SFRP2;    collagen;    stroma;   

DOI  :  10.3389/fonc.2022.834249

来源: DOAJ

【 摘 要 】

BackgroundUrothelial carcinoma (UC) patients often bear clinical and genetic heterogeneity, which may differ in management and prognosis. Especially, patients with advanced/metastatic UC generally have a poor prognosis and survive for only few months. The Wnt/β-catenin signaling is found to be highly activated in several cancers, including UC. However, accumulated evidence has shown discordance between the Wnt/β-catenin signaling and UC carcinogenesis. Accordingly, we aim to get a better understanding of the molecular characterization of UC, focusing on the Wnt signaling, which may add value to guiding management more precisely.Patients and MethodsClinical data and pathological features were retrospectively surveyed. The correlations of secreted Frizzled-related protein 2 (SFRP2) immunoexpression with clinicopathological features were analyzed by Pearson’s chi-square test. The Kaplan–Meier method with a log-rank test was employed to plot survival curves. All significant features from the univariate analysis were incorporated into the Cox regression model for multivariate analysis.ResultsFollowing data mining on a transcriptome dataset (GSE31684), we identified that 8 transcripts in relation to the Wnt signaling pathway (GO: 0016055) were significantly upregulated in advanced/metastatic bladder tumors. Among these transcripts, the SFRP2 level showed the most significant upregulation. Additionally, as SFRP2 is a putative Wnt inhibitor and may be expressed by stroma, we were interested in examining the immunoexpression and clinical relevance of stromal and tumoral SFRP2 in our urothelial carcinoma cohorts containing 295 urinary bladder UC (UBUC) and 340 upper urinary tract UC (UTUC) patients. We observed that high SFRP2 expression in stroma but not in tumors is significantly linked to aggressive UC features, including high tumor stage and histological grade, positive nodal metastasis, the presence of vascular and perineural invasion, and high mitotic activity in UBUC and UTUC. Moreover, high stromal SFRP2 expression significantly and independently predicted worse clinical outcomes in UBUC and UTUC. Utilizing bioinformatic analysis, we further noticed that stromal SFRP2 may link epithelial–mesenchymal transition (EMT) to UC progression.ConclusionCollectively, these results imply that stromal SFRP2 may exert oncogenic function beyond its Wnt antagonistic ability, and stromal SFRP2 expression can provide prognostic and therapeutic implications for UC patients.

【 授权许可】

Unknown