title: Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma.
abstract: It has been reported that tetraspanin CD151 acts as a promoter of metastasis in several tumors and plays an important role in c-Met/hepatocyte growth factor signaling. However, the role of CD151 alone and coexpression of CD151/c-Met in hepatocellular carcinoma (HCC) remains unclear. We found that expression of CD151 was positively related to metastatic potential of HCC cell lines, and modified cells with CD151(high) showed higher secretion of matrix metalloproteinase 9 and aggressiveness in vitro and higher metastatic ability in vivo. Furthermore, HCC patients with vascular invasion, large tumors, multiple tumors, high tumor-node-metastasis stage, and undifferentiated tumor were prone to have higher CD151 expression. The postoperative 3-, 5-, and 7-year overall survival (OS) of patients in HCCs with CD151(high) were significantly lower than those in the CD151(low) group, and correspondingly cumulative recurrence rates in HCCs with CD151(high) were significantly higher than those in the CD151(low) group. Both CD151 and c-Met were remarkably overexpressed in HCCs, compared with adjacent nontumorous and normal liver tissues. Pearson correlation analysis showed a slight correlation between CD151 and c-Met in HCCs. Importantly, the 5- and 7-year OS rates in CD151(high)/c-Met(high) patients were 50.5% and 37.8%, respectively, significantly lower than those of CD151(low)/c-Met(low) patients (63.9% and 54.6%, respectively). Five- and 7-year cumulative recurrence rates in CD151(high)/c-Met(high) patients were 53.3% and 71.9%, respectively, markedly higher than those of CD151(low)/c-Met(low) patients (39.0% and 52.5%, respectively). Multivariate analysis revealed that CD151 and combination of CD151/c-Met were independent prognostic indicators for OS and cumulative recurrence.
  
  
  CONCLUSIONS
  CD151 is positively associated with invasiveness of HCC, and CD151 or combination of CD151/c-Met is a novel marker in predicting the prognosis of HCC and a potential therapeutic target.
authors.affiliation: Experimental Research Center of Zhongshan Hospital, Fudan University, Shanghai, PR China. keaiwu55@yahoo.com.cn
authors.forename: Ai-Wu
authors.initials: AW
authors.lastname: Ke
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Shi
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Fei-Zhen
authors.initials: FZ
authors.lastname: Wu
authors.forename: Zhen-Bin
authors.initials: ZB
authors.lastname: Ding
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Hu
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Zheng-Ji
authors.initials: ZJ
authors.lastname: Song
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Jin-Cai
authors.initials: JC
authors.lastname: Wu
authors.forename: Dou-Sheng
authors.initials: DS
authors.lastname: Bai
authors.forename: Jia-Chu
authors.initials: JC
authors.lastname: Li
authors.forename: Kang-Da
authors.initials: KD
authors.lastname: Liu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060185:Tetraspanin 24; D014162:Transfection
chemical_list: D015703:Antigens, CD; C554715:CD151 protein, human; D012333:RNA, Messenger; D060185:Tetraspanin 24; D019859:Proto-Oncogene Proteins c-met