Loss of p57 expression and RhoA overexpression are associated with poor survival of patients with hepatocellular carcinoma

Tinghua Hu,Shuo Yu,Lili Jiang,Jiequn Ma,Wenjuan Wang,Chengcheng Yang,Lili Han,Hui Guo,Kejun Nan,Qianqian Guo

doi:10.3892/or.2013.2608

Abstract

p57 and Ras homology A (RhoA) have been implicated in the growth and metastasis of several types of human cancers. This study aimed to detect their expression in hepatocellular carcinoma (HCC) tissue specimens and to determine a possible association with clinicopathological data and patient survival. A total of 80 HCC and corresponding distant normal tissue specimens were processed for immunohistochemical and qPCR analyses of p57 and RhoA expression. The data showed that expression of p57 mRNA and protein was reduced in HCC tissues when compared to that in distant non-cancer tissues (P<0.05), while expression of RhoA mRNA and protein was significantly higher in HCC tissue specimens when compared to that of the distant normal tissues. Loss of p57 expression was associated with HCC with higher α-fetoprotein (AFP) levels (>400 ng/ml; P=0.044), larger tumor size (>5 cm, P=0.004), poor tumor differentiation (P=0.020), advanced TNM stage (P=0.027), capsule invasion (P=0.018) and tumor thrombosis (P=0.008), whereas expression of RhoA protein was signiﬁcantly associated with poor tumor differentiation (P=0.042), capsule invasion (P=0.022), and tumor thrombosis (P=0.002). Furthermore, there was a strong inverse relationship between p57 and RhoA expression in HCC tissues, indicating that loss of p57 expression may contribute to RhoA overexpression in HCC tissues. The median survival time of HCC patients with p57+ and p57- expression was 13.0 and 9.0 months, respectively, whereas the median survival time of HCC patients with RhoA+ and RhoA- was 9.0 and 15.0 months. Univariate analysis revealed that the levels of AFP, tumor size, TNM stage, histological grade, capsule invasion, tumor thrombosis, p57, RhoA and co-expression of p57 and RhoA were all significant prognostic indicators for overall survival of HCC patients. Multivariate analysis showed that tumor size, TNM stage, p57, RhoA and combined loss of p57 with RhoA were risk factors for poor survival of HCC patients. This study indicates that the abnormal expression of p57 and RhoA contributes to progression of HCC and poor survival of patients.

Highlights

Hepatocellular carcinoma (HCC) is a significant health issue and is associated with poor prognosis and high mortality, accounting for more than 700,000 new cases and more than 600,000 cancer-related deaths each year worldwide
Our data showed that loss of expression of p57 was associated with HCC with higher α-fetoprotein (AFP) levels (>400 ng/ml; P=0.044), Figure 1. qRT-PCR detection of p57 and Ras homology A (RhoA) mRNA levels in HCC and normal tissue specimens. (A) The relative expression of p57 mRNA in 80 HCC tissues compared with matched distant non-tumor tissues. (B) The relative expression of RhoA mRNA in 80 HCC tissues compared with the distant non-tumor tissues (**P
We found that the combination of the loss of expression of p57 mRNA and protein and overexpression of RhoA mRNA and protein in HCC tissue specimens was significantly more apparent than in distant normal tissues

Summary

Introduction

Hepatocellular carcinoma (HCC) is a significant health issue and is associated with poor prognosis and high mortality, accounting for more than 700,000 new cases and more than 600,000 cancer-related deaths each year worldwide. Half of these new cases and deaths are estimated to occur in China due to the epidemic prevalence of chronic hepatitis B virus infection. Novel approaches or strategies to effectively control progression, detect the disease early, and predict prognosis are international priorities in HCC Towards this end, our research focused on biomarker discovery and identification, and verification of novel biological markers for early detection or prediction of survival and treatment outcome

Objectives

Methods

Results

Conclusion