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

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

doi:10.3892/or.2013.2608

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

Authors:
- Tinghua Hu
- Hui Guo
- Wenjuan Wang
- Shuo Yu
- Lili Han
- Lili Jiang
- Jiequn Ma
- Chengcheng Yang
- Qianqian Guo
- Kejun Nan
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Affiliations: Department of Oncology, The First Afﬁliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 71006, P.R. China, Department of Hepatobiliary and Pancreas Surgery, The First Afﬁliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 71006, P.R. China
Published online on: July 9, 2013 https://doi.org/10.3892/or.2013.2608
Pages: 1707-1714

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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.

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