WISP1 and Mir-29c-3p are Novel Prognostic Biomarkers and Therapeutic Targets for Bladder Cancer

Hongyi Z,Ming Z,Jianfeng S,Zhuo W,Leilei Z Zhuoqun X

doi:10.26502/jcsct.5079135

Abstract

Aberrant expression of WISP1 is associated with carcinogenesis; however, the expression and prognostic values of WISP1 in bladder cancer remain elusive. Therefore, the present study aimed to investigate the WISP1 expression in bladder cancer and explore the possible mechanisms and clinical value of WISP1 in bladder carcinogenesis. The in silico analysis based on oncomine and Kaplan-Meier Plotter databases revealed that WISP1 was up-regulated in bladder cancer and associated with poor survival in patients with bladder cancer. Besides, WISP1 expression was identified to be up-regulated both in bladder cancer tissues and cell lines by qRT-PCR and Western blot assays. Using TargetScan database, we identified 13 miRNAs that putatively regulate the expression of WISP1. Of these miRNAs, only miR-29c-3p was found to be significantly negatively correlated with WISP1 in bladder cancer tissues. The correlation of in situ expressions of WISP1 and miR-29c-3p by immunohistochemistry (IHC) and clinical characteristics revealed that WISP1 was significantly associated with tumor size and hsa-miR-23b- 3p expression, and miR-29c-3p was associated with tumor size, M stage, and WISP1 expression. Multivariate Cox regression analysis indicated that TNM stage and WISP1 expression were predictors of unfavorable prognosis, while hsa-miR-29c-3p was a predictor of favorable prognosis in patients with bladder cancer. Collectively, the findings indicated that WISP1 and miR-29c-3p might serve as novel prognostic biomarkers and potential therapeutic targets for bladder cancer.

Highlights

Bladder cancer(BC) ranks the tenth most frequently diagnosed urological malignancy, with approximately 550,000 new cases diagnosed in 2018 worldwide
Collectively, the findings indicated that WNT1-inducible signaling pathway protein 1 (WISP1) and miR-29c-3p might serve as novel prognostic biomarkers and potential therapeutic targets for bladder cancer (BC)
These results indicated that the aberrant expression of WISP1 in BC was associated with unfavorable survival. quantitative real-time PCR (qRT-PCR) and Western blot analyses of cancer tissues and adjacent normal tissues from BC patients revealed that WISP1 was noticeably up-regulated in BC tissues, as shown in Figure 1c, d/e

Summary

Introduction

Bladder cancer(BC) ranks the tenth most frequently diagnosed urological malignancy, with approximately 550,000 new cases (nearly 425,000 in males and 125,000 in females) diagnosed in 2018 worldwide. It is among the leading causes of cancer-associated mortality, with approximately 200,000 deaths reported in 2018. The molecular mechanisms underlying the occurrence and development of bladder carcinogenesis remain to be completely elucidated. Aberrant expression of WISP1 is associated with carcinogenesis; the expression and prognostic values of WISP1 in bladder cancer (BC) remain elusive. The present study aimed to investigate the WISP1 expression in BC and explore the possible mechanisms and clinical value of WISP1 in BC

Methods

Results

Discussion

Conclusion