Expression of glypican 3 enriches hepatocellular carcinoma development-related genes and associates with carcinogenesis in cirrhotic livers

Xiyong Liu, Sean K. Wang, Keqiang Zhang, Hang Zhang, Qin Pan, Zhiwei Liu, Hongming Pan, Lijun Xue, Yun Yen, Peiguo G. Chu

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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.

Original languageEnglish
Pages (from-to)232-242
Number of pages11
JournalCarcinogenesis
Volume36
Issue number2
DOIs
Publication statusPublished - Aug 20 2014

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Glypicans
Hepatocellular Carcinoma
Carcinogenesis
Liver
Genes
Messenger RNA
Real-Time Polymerase Chain Reaction
Recurrence
Kaplan-Meier Estimate

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

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Expression of glypican 3 enriches hepatocellular carcinoma development-related genes and associates with carcinogenesis in cirrhotic livers. / Liu, Xiyong; Wang, Sean K.; Zhang, Keqiang; Zhang, Hang; Pan, Qin; Liu, Zhiwei; Pan, Hongming; Xue, Lijun; Yen, Yun; Chu, Peiguo G.

In: Carcinogenesis, Vol. 36, No. 2, 20.08.2014, p. 232-242.

Research output: Contribution to journalArticle

Liu, Xiyong ; Wang, Sean K. ; Zhang, Keqiang ; Zhang, Hang ; Pan, Qin ; Liu, Zhiwei ; Pan, Hongming ; Xue, Lijun ; Yen, Yun ; Chu, Peiguo G. / Expression of glypican 3 enriches hepatocellular carcinoma development-related genes and associates with carcinogenesis in cirrhotic livers. In: Carcinogenesis. 2014 ; Vol. 36, No. 2. pp. 232-242.
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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.",
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