Abstract 883: Glutaminases expression and viral infection as potential prognostic factors in cervical, head and neck and liver cancers

Abstract

Abstract Human Papilloma virus (HPV)-associated Cervical squamous cell carcinoma (CESC-HPV(+)), HPV-associated Head and Neck squamous cell carcinoma (HNSCC-HPV(+)), and Hepatitis Virus B/C (HBV/HCV)-associated Liver hepatocellular carcinoma (LIHC-HBV(+)/LIHC-HCV(+)) present metabolic changes during viral transformation to adjust energy demands of transformed cells. Glutamine is used as an important energy and carbon source by cancer cells through its degradation (glutaminolysis). This latter is regulated by Glutaminases 1 and 2 (GLS1/GLS2) that convert glutamine in glutamate. GLS1/2 expression is altered both in HNSCC and LIHC but it is undetermined in CESC. We aimed to indagate if the expression of GLS1/GLS2 genes and/or status of infection by HPV, HBV, and HCV, are associated to the overall survival (OS) in CESC, HNSCC and LIHC. The Cancer Genome Atlas (TCGA) was mined and both gene expression and copy number variation (CNV) of GLS1/GLS2 was analyzed across the CESC, HNSCC and LIHC cohorts. Changes in gene expression were determined by analyzing the Log2FC and by applying statistical analysis (Welch’s T-test or One-Way ANOVA). To learn if the genomic profile was associated with phenotype, gene status was correlated with demographic and clinical data such as age group, ethnicity, race, gender, BMI, viral subtype, histologic grade, clinical stage, and tobacco/alcohol consumption. We applyed chi-squared, one-way ANOVA, and Welch’s T-tests for those assays. Kaplan Meier (K-M) plots were obtained to figure out the association of genomic and phenotypic data with OS. Our results showed that GLS1/GLS2 had no CNVs across the analyzed cohorts. However, GLS1 was upregulated in cancerous tissues both in HNSCC and LIHC (p<0.05, Log2FC>2) whereas GLS2 was downregulated in cancerous tissues in LIHC (p<0.05, Log2FC=-2). Likewise, GLS1 was upregulated both in HNSCC-HPV(-) and LIHC-HBV/HCV(+) compared with HNSCC-HPV(+) and LIHC-HBV/HCV(-), respectively (p<0.05). Also, GLS2 was over-expressed in CESC-HPV(+) and HNSCC-HPV(+) patients, compared with CESC-HPV(-) and HNSCC-HPV(-) patients, respectively (p<0.05). In the other hand, GLS2 was under-expressed in LIHC-HBV/HCV(+) compared with LIHC-HBV/HCV(-) patients (p<0.05, Log2FC = -2.5). Finally, K-M plots showed that GLS2 expression is associated with OS in CESC patients whereas the HPV subtypes and HBV/HCV infection were associated with OS in HNSCC and LIHC patients, respectively (p<0.05). We concluded that the expression of glutaminases is abnormal in patients with CESC, HNSCC, and LIHC and it depends on the status of viral infection. Since the GLS2 expression and viral infection affects the OS in the analyzed tumors, our research provides with potential prognostic markers of CESC, HNSCC and LIHC that should be validated in future studies. Citation Format: Livisu Pajares Rojas, Claudia Machicado Rivero. Glutaminases expression and viral infection as potential prognostic factors in cervical, head and neck and liver cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 883.