title: Loss of p57 expression and RhoA overexpression are associated with poor survival of patients with hepatocellular carcinoma.
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.
authors.affiliation: Department of Oncology, The First Afﬁliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 71006, P.R. China.
authors.forename: Tinghua
authors.initials: T
authors.lastname: Hu
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.forename: Shuo
authors.initials: S
authors.lastname: Yu
authors.forename: Lili
authors.initials: L
authors.lastname: Han
authors.forename: Lili
authors.initials: L
authors.lastname: Jiang
authors.forename: Jiequn
authors.initials: J
authors.lastname: Ma
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Yang
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Guo
authors.forename: Kejun
authors.initials: K
authors.lastname: Nan
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000172:deficiency / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D013534:Survival; D055815:Young Adult; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D012333:RNA, Messenger; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein