FGFR4 and TGF-β1 Expression in Hepatocellular Carcinoma: Correlation with Clinicopathological Features and Prognosis

Abstract

Objective: To investigate the expression and correlation of transforming growth factor-β1 (TGF-β1) and fibroblast growth factor receptor 4 (FGFR4) in human hepatocellular carcinoma (HCC) and the relationship with clinicopathological features and prognosis.Materials and methods: The expression of TGF-β1 and FGFR4 in 126 HCC samples was detected immunohistochemically. Combined with clinical postoperative follow-up data, the expression of TGF-β1 and FGFR4 in HCC and the relationship with the prognosis of patients were analyzed by statistically.Results: The positive expression rate of TGF-β1 was 84.1% (106/126) in tumors, and that in peritumoral liver tissues was 64.3% (81/126); the positive expression rate of FGFR4 in tumors was 74.6% (94/126) and that in peritumoral liver tissues was 57.1% (72/126). The expression of TGF-β1 and FGFR4 in the carcinoma tissues was significantly higher than that in peritumoral liver tissues (p < 0.05). Intratumoral TGF-β1 and FGFR4 expression was associated with TNM stage (p < 0.05). TGF-β1 and FGFR4 expression levels didn't significantly correlate with other clinicopathological parameters, including age, sex, tumor size, serum AFP level, tumor differentiation, lymph node metastasis, etc. (p > 0.05). TGF-β1 expression was positively correlated with FGFR4 expression (r = 0.595, p < 0.05). Patients with positive FGFR4 or TGF-β1 expression had shorter overall survival compared with negative expression (p < 0.05).Conclusions: The expression of TGF-β1 and FGFR4 could make synergy on the occurrence and progression of HCC, and may be used as prognosis indicators for HCC patients.

Article Commentary: TGF-β Mediated Crosstalk between Malignant Hepatocyte and Tumor Microenvironment in Hepatocellular Carcinoma

“…However, aberrant expression of FGFs has been reported in HCC, and it has been found to promote HCC and endothelial cell proliferation through the activation of downstream ERK and AKT pathways. Chen et al showed comparative positive expression rate of TGF-β1 [84.1% (106/126) in hepatic tumors and 64.3% (81/126) in peritumoral liver tissues] and FGFR4 [74.6% (94/126) in hepatic tumors and 57.1% (72/126) in peritumoral liver tissues] in hepatic tumors and peritumoral liver tissues 75. The long-term exposure to TGF-β in paracrine way induces isoform switching of FGFR and sensitizes the cells to FGF-2.…”

High Serum Transforming Growth Factor-β1 Levels Predict Outcome in Hepatocellular Carcinoma Patients Treated with Sorafenib

“…Previous studies have reported that TGF-b1 was overexpressed in HCC (12,13). In established HCC cells, TGF-b1 promoted EMT, triggered migration and invasion, and induced an aggressive phenotype by reducing E-cadherin expression (14,15).…”

TGF-β1 Promotes Hepatocellular Carcinoma Invasion and Metastasis via ERK Pathway-Mediated FGFR4 Expression

“…Our previous work showed that FGFR4 expression was associated with the prognosis of HCC and was correlated with TGF-β expression [19]. Using immunohistochemistry (IHC) and clinical postoperative follow-up data, we assessed crosstalk between FGFR4 and TGF-β1 in HCC.…”

“…Our previous work shows synergism with respect to the occurrence and progression of HCC according to clinicopathological features and patient prognosis [19]. In this study, we furthered studied the cooperation of FGFR4 and TGF-β1 in the invasion and metastasis of HCC; TGF-β1 promoted the invasion and metastasis of HCC by inducing FGFR4 expression in vitro and in vivo , and the ERK pathway was involved.…”