title: Identification of Gem as a new candidate prognostic marker in hepatocellular carcinoma.
abstract: GTP binding protein overexpressed in skeletal muscle (Gem) is a Ras-related protein whose expression is induced in several cell types upon activation by extracellular stimuli. To investigate the potential roles of Gem in hepatocellular carcinoma (HCC), expression of Gem was examined in human HCC samples. Western blot analysis showed that compared with primary human hepatocytes and adjacent noncancerous tissue, significant down-regulation of Gem was found in HCC cells and tumor tissues. In addition, immunohistochemical analysis of Gem expression was investigated in 108 specimens of HCC tissues. Clinicopathological data were collected to analyze the association with Gem expression. Expression of Gem was significantly negatively correlated with histological grade (P=0.001), tumor size (P=0.020), and vascular invasion (P=0.005), and Gem was also negatively correlated with proliferation marker Ki-67 (P<0.01). More importantly, the Kaplan-Meier survival curves analysis revealed that low expression of Gem was associated with poor prognosis in HCC patients. Univariate analysis showed that Gem expression was associated with poor prognosis (P=0.006). Multivariate analysis indicated that Gem expression was an independent prognostic marker for HCC (P=0.007). Finally, serum starvation and release experiments showed that Gem expression was negatively related with cell proliferation. In the conclusion, our results suggested that down regulation of Gem expression was involved in the pathogenesis of hepatocellular carcinoma, and it might be a favorable independent prognostic parameter for HCC.
authors.affiliation: Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu 226001, PR China; Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Cong
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Dunpeng
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Pathology, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu 226001, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu 226001, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Changyun
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China. Electronic address: nirunzhou@sina.cn.
authors.forename: Runzhou
authors.initials: R
authors.lastname: Ni
authors.affiliation: Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu 226001, PR China. Electronic address: zhangyixin881125@126.com.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: Cell cycle; GTP binding protein overexpressed in skeletal muscle (Gem); Hepatocellular carcinoma (HCC); Prognosis; Proliferation