Abstract
Introduction/Objectives: Hepatitis C virus (HCV) infection affects millions globally and remains a leading cause of cirrhosis and hepatocellular carcinoma (HCC). While different biomarkers for HCV progression are currently being researched, there is little known about sex-based biomarkers. It is significant to acknowledge sex-based differences in diseases especially due to previous research that showed liver estrogen receptor (ER)-mediated sex-based differences exist in cirrhosis and HCC patients. Liver ER-binding may lead to protective effects in pre-menopausal women. Showing that there were sex-based differences led us to investigate the glycogen phosphorylase enzyme family, specifically the liver isoform (PYGL). It plays a key role in glycogen metabolism. Dysregulation of PYGL has been studied in different cancers, yet its role in sex-based differences in HCV-induced cirrhosis and HCC remains unexplored. This study aimed to evaluate the sex-based differential expression of PYGL and its potential role as a biomarker in HCV-induced cirrhosis and HCC progression.
Methods: 65 (healthy, cirrhosis, HCC) liver tissues were obtained from NIH Liver Tissue Bank. DIA proteomics mapped 4445 proteins, including PYGL. Immunohistochemistry (IHC) validated PYGL protein expression in these tissues.
Results: From the proteomics study, PYGL is not upregulated in HCV-cirrhosis males compared to healthy controls but shows significant upregulation in HCV-cirrhosis females, highlighting sex-based differences. In HCC patients, PYGL is significantly upregulated regardless of sex, with no observed differences between males and females. From IHC, PYGL expression was confirmed to be present in all three tissue types across both sexes.
Conclusions: PYGL was upregulated in HCC patients in comparison to controls. This upregulation should be investigated to see if the upregulation is specific to the liver or the tumor itself. Elevated PYGL expression in females may serve as a biomarker for early-stage HCV-related liver disease progression to hepatocellular carcinoma.
Methods: 65 (healthy, cirrhosis, HCC) liver tissues were obtained from NIH Liver Tissue Bank. DIA proteomics mapped 4445 proteins, including PYGL. Immunohistochemistry (IHC) validated PYGL protein expression in these tissues.
Results: From the proteomics study, PYGL is not upregulated in HCV-cirrhosis males compared to healthy controls but shows significant upregulation in HCV-cirrhosis females, highlighting sex-based differences. In HCC patients, PYGL is significantly upregulated regardless of sex, with no observed differences between males and females. From IHC, PYGL expression was confirmed to be present in all three tissue types across both sexes.
Conclusions: PYGL was upregulated in HCC patients in comparison to controls. This upregulation should be investigated to see if the upregulation is specific to the liver or the tumor itself. Elevated PYGL expression in females may serve as a biomarker for early-stage HCV-related liver disease progression to hepatocellular carcinoma.
| Original language | American English |
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| State | Published - 14 Feb 2025 |
| Event | Oklahoma State University Center for Health Sciences Research Week 2025 - Oklahoma State University Center for Health Sciences, Tulsa, United States Duration: 10 Feb 2025 → 14 Feb 2025 https://medicine.okstate.edu/research/research_days.html |
Conference
| Conference | Oklahoma State University Center for Health Sciences Research Week 2025 |
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| Country/Territory | United States |
| City | Tulsa |
| Period | 10/02/25 → 14/02/25 |
| Internet address |