High TGF-β1 expression predicts poor disease prognosis in hepatocellular carcinoma patients

Li Peng,Chao-Yang Zhang,Fei Ye,Zhao-Yang Liu,Guan-Cheng Li,Xi Pan,Xiao-Qing Yuan,Hui-Fang Zhou,Ya-Qin Zhang,Wen-Ling Li

doi:10.18632/oncotarget.16166

Abstract

Transforming growth factor beta (TGF-β) promotes the pathogenesis of hepatocellular carcinoma (HCC). We evaluated the associations between TGF-β1 expression and clinicopathological parameters in HCC patients from The Cancer Genome Atlas (TCGA), as well as the prognostic power of TGF-β1 expression. Eligible studies were retrieved from several databases, and effects (hazard ratios (HRs) with 95% confidence intervals (CIs)) for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), metastasis-free survival (MFS), and progression-free survival (PFS) were pooled to assess the prognostic ability of TGF-β1 expression in HCC patients. Twelve qualified articles and our TCGA data comprising 2,021 HCC patients were incorporated. In the TCGA analysis, HCC patients with higher TGF-β1 expression presented a shorter OS than those with lower TGF-β1 expression (HR = 1.42, p < 0.05). In the meta-analysis, univariate analyses showed that HCC patients with higher TGF-β1 expression had a shorter OS (pooling HR = 1.71, p < 0.01) and DFS/RFS/MFS/PFS (pooling HR = 1.60, p < 0.01) than those with lower TGF-β1 expression. In conclusion, our results suggested that high TGF-β1 expression promotes a poor prognosis in HCC patients.

Highlights

Hepatocellular carcinoma (HCC) is a common neoplasm of the estimated 782,000 new cancer cases worldwide (50% in China alone), as well as the third leading cause of death from cancer worldwide with nearly 745,000 deaths in 2012 [1, 2]
High TGF-β1 expression predicted a poor prognosis in hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas (TCGA)
TGF-β1 expression can help primary carcinoma cells migrate and disseminate to distant sites [22,23,24]. This metastasis contributes to high mortality of hepatocellular carcinoma (HCC) [25,26,27,28], which is the third dominating cause of cancer-related deaths worldwide [29,30,31,32]

Summary

Introduction

Hepatocellular carcinoma (HCC) is a common neoplasm of the estimated 782,000 new cancer cases worldwide (50% in China alone), as well as the third leading cause of death from cancer worldwide with nearly 745,000 deaths in 2012 [1, 2]. TGF-β orchestrates a favorable microenvironment for cancer cell growth and progression of the epithelial - mesenchymal transition (EMT) [6] and promotes fibrogenesis [7, 8], suggesting TGF-β stimulates HCC pathogenesis and metastasis. TGF-β signaling inhibitors could hinder HCC cell growth and progression by inhibiting the EMT process in distinct experiment models, leading to the clinical investigation of the TGF-β inhibitor LY2157299 (phase II clinical trial, Identifier: NCT01246986, http://clinicaltrials.gov) [6, 9]. Whether TGF-β1 expression has the potential to predict HCC prognosis is inconsistent. There is a need to implement meta-analysis and larger sample evaluation, aiming to systematically elaborate on the prognostic power of TGF-β1 expression in HCC patients

Methods

Results

Conclusion