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Objective: The study aims to explore the prognostic significance of zona pellucida glycoprotein 3 (ZP3) in hepatocellular carcinoma (HCC) tissues. Methods: The expression of ZP3 protein in HCC tissues was detected by immunohistochemistry (IHC) to study its effects on the clinicopathological characteristics and prognosis of HCC patients. The Cancer Genome Atlas (TCGA) database was used to confirm the expression of ZP3 in HCC tissues, and Gene set enrichment analysis (GSEA) was performed to obtain potential ZP3-related pathways in HCC. Results: IHC detection found that ZP3 had a high expression in HCC tissues and was associated with cirrhosis and hepatitis B virus infection in HCC patients (p<0.05). TCGA database also showed that ZP3 was up-regulated in HCC tissues. Further survival evaluation confirmed that ZP3 expression caused an impact on the overall survival time and disease-free survival time of HCC patients (p<0.05), implying a potential role in HCC prognosis. GSEA analysis indicated that the 187 differential gene sets were mainly involved in 10 signaling pathways, including 5 up-regulated and 5 down-regulated pathways. Conclusion: High expression of ZP3 in HCC tissues is found to have an important role in HCC development and prognosis.

Abstract: Objective: It has been recognized that HBV infection and alcohol consumption are two important risk factors for primary hepatocellular carcinoma (HCC). Recently, the role of clonorchiasis as a risk factor for HCC is controversial. We aimed to investigate whether these factors increase the risk of HCC in Guangxi, China. Methods: A hospital-based, case-control study of HCC was conducted from July 2005 to July 2007. We enrolled 500 consecutive patients with HCC as an experimental group and 500 patients without tumor in liver as a control group. The risk factors that the patients were exposed to were assessed. Results: Comparing the risks of developing the HCC, we found out the following results. The risk of developing HCC for the patients with clonorchiasis was 5 folds of that for the patients without clonorchiasis (OR = 5.0; 95% CI: 3.1–8.1), and the risk for the patients with alcohol consumption was 3 folds of that for the patients without drinking alcohol (OR = 3.4; 95% CI: 2.3–4.9), and similarly, the risk for the patients with HBV infection was 21 times of that for the patients without HBV infection (OR = 20.6; 95% CI: 14.3–29.7). According to crossover analysis, there was significant interaction among clonorchiasis, HBV infection and alcohol consumption, with synergistic indices greater than 1. The etiologic fractions attributed to these interactions [EF (A × B)] are 0.7465, 0.5789 and 0.5506, respectively. Conclusion: Clonorchiasis, HBV infection and heavy alcohol consumption are independent risk factors for developing HCC in our population in Guangxi, and as they can interact synergistically, the risk of developing HCC is increased. Data from this study may indicate new prevention strategies of developing HCC in high-risk individuals.