Abstract

BackgroundEmbryonic Liver Fodrin (ELF) is an adaptor protein of transforming growth factor (TGF-β) signaling cascade. Disruption of ELF results in mislocalization of Smad3 and Smad4, leading to compromised TGF-β signaling. c-Myc is an important oncogenic transcription factor, and the disruption of TGF-β signaling promotes c-Myc-induced hepatocellular carcinoma (HCC) carcinogenesis. However, the prognostic significance of c-Myc in HCC is less understoodMethodsThe expression of c-Myc protein and mRNA were measured by immunohistochemistry (IHC) and qRT- PCR, respectively. IHC was performed to detect TGF-β1 and ELF expression in HCC tissues. Their relationship with clinicopathological factors and overall survival (OS) and disease free survival (DFS) were examined.ResultsThe expression of c-Myc protein and mRNA in HCC tissues were significantly higher in HCC area than those in normal liver tissues. However, the expression were low compared with those adjacent to HCC area. c-Myc protein was independently predictive of DFS and OS, and it was negatively correlated with tumor size (P = 0.031), tumor number (P = 0.038), and recurrence (P = 0.001). Low c-Myc expression was associated with short-term recurrence and poor prognosis. The predictive value of c-Myc combined with TGF-β1 or/and ELF was higher than that of any other single marker. Low c-Myc, high TGF-β1 or/and low ELF expression was associated with the worst DFS and OS.ConclusionsLow expression of c-Myc protein predicts poor outcomes in patients with HCC with hepatectomy. The combination of the expression of c-Myc, TGF-β1, and ELF can be used to accurately predict outcomes of patients with HCC.

Highlights

  • Embryonic Liver Fodrin (ELF) is an adaptor protein of transforming growth factor (TGF-β) signaling cascade

  • We observed that the levels of c-myc mRNA in hepatocellular carcinoma (HCC) tissues and in adjacent tissues were higher than that in normal liver tissues (P = 0.002 and P < 0.001, respectively)

  • We found the level of c-myc mRNA in HCC tissues was remarkably lower than those in the corresponding adjacent tissue (P < 0.001)

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Summary

Introduction

Embryonic Liver Fodrin (ELF) is an adaptor protein of transforming growth factor (TGF-β) signaling cascade. C-Myc is an important oncogenic transcription factor, and the disruption of TGF-β signaling promotes c-Mycinduced hepatocellular carcinoma (HCC) carcinogenesis. Hepatocellular carcinoma (HCC) is a very common and serious malignancy with high morbidity and high mortality. It is the sixth most common cancer and the third common cause of cancer-related death worldwide [1,2,3]. C-Myc, an important oncogenic transcription factor, locates on chromosome 8q24.1, and involves in cell proliferation, apoptosis, differentiation and metabolism because it participates in the regulation of 15% of all genes in the human genome, including microRNAs [6,7,8,9,10,11,12]. As a powerful cancer-promoting oncogene, c-Myc has been implicated in the pathogenesis of kinds of malignant tumors, including human solid tumor, leukemia and

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