TMPRSS4 as an emerging potential poor prognostic factor for solid tumors: A systematic review and meta-analysis.

Ping Zeng,Yi-Xin Shen,Peng Zhang,Min-Bin Chen,Li-Na Zhou,Ya-Qun Zhu,Jun Jin,Min Tang

doi:10.18632/oncotarget.10153

Abstract

Recent studies have investigated the potential prognostic value of the transmembrane protease serine 4 (TMPRSS4) in various solid tumors. Yet, the results are inconclusive. Here, we performed this meta-analysis to clarify this issue. Relevant articles were identified by searching PubMed, Web of Science and Embase databases. The primary outcome endpoints were patients' overall survival (OS) and time to tumor progression (TTP). Twelve studies involving 1,955 participants were included. We showed that high TMPRSS4 expression in tumor tissues was significantly associated with patients' poor OS (pooled HR = 2.981, 95% CI = 2.296-3.869, P < 0.001) and short TTP (pooled HR = 2.456, 95% CI = 1.744-3.458, P < 0.001). A subgroup analysis revealed that the association between TMPRSS4 and the outcome endpoints (OS or TTP) was also significant within China region. We conclude that TMPRSS4 overexpression in solid tumors is associated with patients' poor prognosis. TMPRSS4 could be a valuable prognosis biomarker or a promising therapeutic target of solid tumor.

Highlights

The transmembrane protease serine 4 (TMPRSS4) is a single-pass type II membrane protein and a novel serine protease [1]
The results showed that TMPRSS4 overexpression was associated with poor overall survival (OS) of solid tumors (Figure 2)
Up to now, no meta-analyses have been performed to evaluate the prognostic value of TMPRSS4 expression in the tumor patients

Summary

Introduction

The transmembrane protease serine 4 (TMPRSS4) is a single-pass type II membrane protein and a novel serine protease [1]. Several TMPRSS4 specific substrates have been identified far, including hemagglutinin of the influenza virus (a protein that is vital for virus infection) [2] and the urokinase-type plasminogen activator (uPA), the latter is important for cancer cell invasion [1, 3]. Inhibition of TMPRSS4 reduced migration and invasion of lung and colon cancer cells [9, 14]. Knockdown of TMPRSS4 by targeted shRNA inhibited proliferation of lung cancer cells [15]. TMPRSS4 overexpression was shown to activate several important pro-cancerous signalling cascades, including focal adhesion kinase (FAK), ERK1/2, Akt, Src and Rac pathways [7]. PI3K or Src inhibitors were shown to inhibit invasiveness of TMPRSS4-overexpressing cells [7]

Methods

Results

Conclusion