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Al B. Benson III, MD, FACP, FASCO

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ASCOBT 2023: Investigating Hypoxia-Induced Mechanisms of PD-L1 Inhibitor Resistance in Liver Cancer

By: Joshua D. Madera, MD
Posted: Monday, August 28, 2023

According to a presentation given at the 2023 American Society of Clinical Oncology (ASCO) Breakthrough meeting (Abstract 158) in Yokohama, Japan, three regulatory genes involved in the intricate mechanism underlying resistance against PD-L1 inhibitors were identified. Specifically, this study focused on the impact of hypoxia-induced changes on PD-L1 expression within the tumor microenvironment. The study findings may guide additional investigative efforts focused on combating PD-L1 inhibitor resistance to promote the development of therapeutic strategies for treating patients with unresectable hepatocellular carcinoma, explained Chan et al, of Health Technology and Informatics, Hong Kong, and colleagues.

Gene-expression profiles (GSE 14520 and GSE 41666) were obtained from the Gene Expression Omnibus and used for bioinformatic analysis. A total of 214 analyses compared hepatocellular carcinoma tumor tissue with normal adjacent tissue, and 6 analyses compared normoxia with anoxia HepG2 cells. Genetic expression was assessed and characterized as either hepatocellular carcinoma signature genes or hypoxia-related genes. In addition, potential regulatory genes and hub genes were investigated using a protein-protein interaction network.

The study authors identified 52 overlapping genes between hepatocellular carcinoma–signature and hypoxia-related differentially expressed genes. Gene-set enrichment analysis revealed five genes associated with the PD-L1 expression pathways. Moreover, 14 PD-L1 regulatory genes and 10 hub genes were found through multiple regression analysis and in the protein-protein interaction network, respectively. Ultimately, three genes were deemed as potential regulatory genes that may affect PD-L1 expression: DLGAP5, KIF20A, and TPX2.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.


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