Abstract

BackgroundTumor suppression of Transforming Growth Factor (TGF-β) signaling pathway requires an adaptor protein, Embryonic Liver Fodrin (ELF). Disruption of ELF expression resulted in miscolocalization of Smad3 and Smad4, then disruption of TGF-β signaling. However, the prognostic significance of ELF for hepatocellular carcinoma (HCC) hasn’t been clarified. This study aimed to investigate whether measuring both TGF-β1 and ELF provides a more powerful predictor for HCC prognosis than either marker alone.MethodsTGF-β1 and ELF protein were detected by immunohistochemistry. The relationship between TGF-β1/ELF expression and patients’ clinicopathologic factors was analyzed. The association between TGF-β1/ELF expression and disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses.ResultsThe expression of TGF-β1 in HCC tissues was significantly higher than that in normal liver tissues. Conversely, the expression of ELF in HCC tissues declined markedly. ELF protein was correlated with HBsAg, tumor size, tumor number, TNM and recurrence. Data also indicated a significant negative correlation between ELF and TGF-β1. Patients with high TGF-β1 expression or/and low ELF expression appeared to have a poor postoperative disease-free survival and overall survival compared with those with low TGF-β1 expression or/and high ELF expression. Furthermore, the predictive range of ELF combined with TGF-β1 was more sensitive than that of either one alone.ConclusionsTGF-β1 and ELF protein are potential and reliable biomarkers for predicting prognosis in HCC patients after hepatic resection. Our current study has demonstrated that the prognostic accuracy of testing can be enhanced by their combination.

Highlights

  • Tumor suppression of Transforming Growth Factor (TGF-β) signaling pathway requires an adaptor protein, Embryonic Liver Fodrin (ELF)

  • The expression rate of TGF-β1 in hepatocellular carcinoma (HCC) tissues (59.5%, 50/84) was significantly higher than that in the normal liver tissues (0, 0/20, P < 0.001), but not in HCC adjacent tissues (46.4%, 39/84, P = 0.089, Table 2, Figure 1A, C). These results suggested that there was the low expression of ELF and high expression of TGF-β1 in HCC tissues

  • Collecting, the results indicated that the combination of TGF-β1 elevation and ELF reduction in HCC tissues appears to be predictive of the poorest prognosis

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Summary

Introduction

Tumor suppression of Transforming Growth Factor (TGF-β) signaling pathway requires an adaptor protein, Embryonic Liver Fodrin (ELF). This study aimed to investigate whether measuring both TGF-β1 and ELF provides a more powerful predictor for HCC prognosis than either marker alone. 60% to 70% of patients develop recurrence or metastasis within 5 years after resection [4,5]. The transforming growth factor β (TGF-β) signaling pathway is known to play an important role in multiple cellular processes, including cell growth, differentiation, adhesion, migration, apoptosis, extracellular matrix formation and immunosuppressant [6,7,8,9].

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