Loss of p57 expression and RhoA overexpression are associated with poor survival of patients with hepatocellular carcinoma
Loss of p57 expression and RhoA overexpression are associated with poor survival of patients with hepatocellular carcinoma
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p57 表达缺失和 RhoA 过度表达与肝细胞癌患者生存率低相关
DOI：
10.3892/or.2013.2608
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发表时间：
2013-10-01
期刊：
影响因子：
4.2
通讯作者：
Nan, Kejun
中科院分区：
文献类型：
--
作者：
Hu, Tinghua;Guo, Hui;Nan, Kejun
p57和Ras同源性A（RhoA）已经涉及几种类型的人类癌症的生长和转移。本研究旨在检测它们在肝细胞癌（HCC）组织标本中的表达，并确定其与临床病理学数据和患者生存率的可能相关性。共80例HCC和相应的远端正常组织标本进行p57和RhoA表达的免疫组化和qPCR分析。结果显示，与远处非癌组织相比，HCC组织中p57 mRNA和蛋白的表达均降低（P400 ng/ml; P=0.044），肿瘤尺寸较大（>5 cm，P=0.004），肿瘤分化差（P=0.020），晚期TNM分期（P=0.027），包膜浸润（P=0.018）和肿瘤血栓形成（P=0.008），而RhoA蛋白表达与肿瘤分化不良显著相关（P=0.042）、包膜侵犯（P=0.022）和肿瘤血栓形成（P=0.002）。此外，在HCC组织中，p57和RhoA表达之间存在强烈的负相关性，表明p57表达的缺失可能有助于HCC组织中RhoA的过表达。p57+和p57-表达的HCC患者的中位生存时间分别为13.0和9.0个月，而RhoA+和RhoA-表达的HCC患者的中位生存时间分别为9.0和15.0个月。单因素分析显示，AFP水平、肿瘤大小、TNM分期、组织学分级、包膜侵犯、癌栓形成、p57、RhoA以及p57和RhoA的共表达均是影响肝癌患者总生存率的重要预后指标。多因素分析显示，肿瘤大小、TNM分期、p57、RhoA以及p57和RhoA联合缺失是影响肝癌患者生存率的危险因素。本研究提示p57和RhoA的异常表达与HCC的进展及患者的生存率有关。
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 (P400 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.