title: Expression of glypican 3 enriches hepatocellular carcinoma development-related genes and associates with carcinogenesis in cirrhotic livers.
abstract: Glypican-3 (GPC3) protein expression was determined by immunohistochemical analysis from 29 normal livers, 80 cirrhotic livers sample taken near hepatocellular carcinoma (HCC), and 87 cirrhotic livers without HCC. The levels for miR-657 and HCC-related gene mRNAs were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Also, a published microarray dataset was used for gene set enrichment analysis (GSEA) to investigate the relationship between GPC3- and HCC-related gene signatures. Kaplan-Meier analysis was used to evaluate the relationship between GPC3 and HCC recurrence. GPC3 protein expression was not detected in any of the 29 (0%) normal livers, but was detected in 32 of 87 (37%) cirrhotic livers without HCC, and 51 of 80 (64%) cirrhotic liver samples taken near HCC sites (P < 0.001). The GPC3-positive rate in cirrhotic livers of viral origin was 68% (27/40), which was significantly higher than for non-viral cirrhotic livers (11%, 5/47) (P < 0.001). Also, GPC3 expression positively correlated with mRNA expression of HCC-related genes in the qRT-PCR and GSEA evaluations. Furthermore, HCC recurrence in cirrhotic liver samples taken near HCC sites was significantly higher in the GPC3-positive group than the GPC3-negative group (Log-rank P = 0.02, HR = 3.26; 95% CI = 1.20-10.29). This study demonstrated that highly expression of GPC3 could enrich HCC-related genes' mRNA expression and positive associate with dysplasia in cirrhotic livers. Therefore, GPC3 may serve as a precancerous biomarker in cirrhotic livers.
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Sean K
authors.initials: SK
authors.lastname: Wang
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China and.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China and.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China and.
authors.forename: Hongming
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute, Taipei Medical University, Taipei, Taiwan (R.O.C) pchu@coh.org.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA, pchu@coh.org.
authors.forename: Peiguo G
authors.initials: PG
authors.lastname: Chu
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D053673:Glypicans / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C105937:GPC3 protein, human; D053673:Glypicans; C582070:MIRN657 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger