Abstract

BackgroundThe 5-year survival rate of patients with hepatocellular cancer (HCC) was very low because of invasion and metastasis in the early stage. Biomarkers might help predict early occurrence of invasion and metastasis. Accumulating evidence has shown that deleted in liver cancer-1 (DLC1) may be considered as a metastasis suppressor gene in numerous solid and hematological cancers. However, its prognostic role and mechanisms that regulate and coordinate these activities remain poorly understood.MethodsWith the method of immunohistochemistry, the expression of DLC-1 as well as Rho A, ROCK2, moesin had been characterized in 80 HCC tissues and adjacent noncancerous tissues. The correlation between their expression and their relationships with clinicopathological characteristics of HCC were also investigated. In addition, the prognostic value of DLC1 expression within the tumor tissues was assessed by Cox regression and Kaplan-Meier analysis.Results DLC1 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues, and DLC-1 expression was found to be negatively correlated with tumor differentiation, TNM stage and lymph node metastasis. Furthermore, DLC-1 expression was found to inversely correlate with Rho A, ROCK2 and moesin which were all highly expressed in HCC tissues. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in HCC patients with higher DLC1 expression, compared to those with lower expression of DLC1. Multivariate Cox proportional hazard analyses revealed that DLC1 was an independent factor affecting the overall survival probability.ConclusionDLC1 could be served as a tumor suppressor gene in the progression especially in the invasion and metastasis of HCC. DLC1 perhaps played its role by regulating the expression of Rho A, ROCK2 and moesin. Evaluation of the expression of DLC-1 might be a good prognostic marker for patients with HCC.

Highlights

  • The 5-year survival rate of patients with hepatocellular cancer (HCC) was very low because of invasion and metastasis in the early stage

  • deleted in liver cancer-1 (DLC1) perhaps played its role by regulating the expression of Rho A, ROCK2 and moesin

  • The expression of Deleted in liver cancer-1 (DLC-1), Rho A, ROCK2 and moesin proteins in liver cancer tissues The cellular locations of DLC-1, Rho A, ROCK2 and moesin proteins were all mainly found in the cytoplasm

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Summary

Introduction

The 5-year survival rate of patients with hepatocellular cancer (HCC) was very low because of invasion and metastasis in the early stage. Biomarkers might help predict early occurrence of invasion and metastasis. Accumulating evidence has shown that deleted in liver cancer-1 (DLC1) may be considered as a metastasis suppressor gene in numerous solid and hematological cancers. Liver cancer is one of the most common malignancies in China and the 5-year survival rate of it is very low because of invasion and metastasis in the early stage [1, 2]. Deleted in liver cancer-1 (DLC-1) was first cloned by using subtractive hybridization method in human hepatocellular carcinomas and later it was identified as a breast cancer metastasis suppressor in microarray comparisons between breast cancer cell lines [4, 5]. Data showed that DLC-1 mRNA expression was lost in 95 % of patient with NSCLC tumors tissues and 58 % of NSCLC cell lines, due at least in part through its function as

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