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.

Advances in the study of oncofetal antigen glypican-3 expression in HBV-related hepatocellular carcinoma

“…Basic and clinical studies have indicated that GPC-3 is a specific indicator of the prognosis for HCC (45). As expected, the overexpression of hepatic GPC-3 was significantly related to the 5-year survival of 69 patients with HCC (p < 0.001).…”

Regulation of hepatocyte identity and quiescence

“…However, accumulating evidence suggest that hepatic insufficiency cannot be only ascribed to the loss of liver parenchyma and the circulatory alterations caused by fibrosis, but also to the gradual decrease in the expression of hepato-specific genes [8,10,86,172]. These alterations in the cirrhotic liver are frequently accompanied by unrestrained cell proliferation and the upregulation of genes characteristic of fetal and transformed hepatocytes, such as WT1, gankyrin and as recently reported the HCC marker glypican-3 [10,13,14,88,173] (Fig. 2).…”

“…The detection of these genes may have potential value as biomarkers and predictors of the clinical course of the neoplastic disease [87]. However, in certain cases, their reactivation already occurs in pre-neoplastic liver lesions [10,88], and some of them may have profound functional implications in the carcinogenic process [86,89,90] (Fig. 2).…”

Atrazine exposure elicits copy number alterations in the zebrafish genome

“…Histidine decarboxylase is the only enzyme that converts histidine to histamine, which is an important bioamine that contributes to inflammation, allergies, and neurotransmission (Ku et al, 2014). Although not investigated as predominately as the neuroendocrine dysfunction caused by atrazine, the inflammatory and immune responses are currently under investigation (Ma et al, 2015; Thompson et al, 2015; Zhao et al, 2013). As hdc expression is predominantly altered in adult male brain tissue, these data could provide support for further studies investigating the immune responses later-in-life following an embryonic atrazine exposure.…”