Prognosis, immunotherapy and drug therapy of oxidative stress-related genes in patients with hepatocellular carcinoma

S.-S. Xiong

Departments of Pharmacology, School of Pharmacy, Qingdao University Medical College, Qingdao, China. 2019021017@qdu.edu.cn

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• Oncology
• Pharmacology

OBJECTIVE: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death, with high morbidity and low survival. Research on the relationship between cancer cells and oxidative stress has rapidly increased in recent years. Therefore, finding new therapeutic and prognostic targets for hepatocellular carcinoma based on oxidative stress-related genes (OSRGs) has far-reaching significance.

MATERIALS AND METHODS: We first obtained OSRGs on GeneCards and then, based on the TCGA database, compared tumor tissues with normal tissues. Using the LASSO Cox regression method, we obtained six differentially expressed genes associated with prognosis. We also divided all HCC patients in the TCGA cohort into a low-risk group and a high-risk group based on these six genes and accordingly performed a correlation analysis of differentially expressed oxidative-stress-related genes (DEOSRGs). These analyses included GSEA, PPI, survival analysis, immune correlation analysis, tumor microenvironment correlation analysis, m6A analysis, gene mutation analysis, drug-sensitivity analysis, and molecular docking validation. The reliability of the model genes was further verified using a multi-platform database, qRT-PCR and MTT assay.

RESULTS: These six genes may play an important role in the prognosis of hepatocellular carcinoma patients by affecting the kinase, carboxylic acid synthesis and metabolism, ROS production, lipid oxidation and immune response. Validation experiment results further confirm that these model genes are good indicators for the diagnosis and prognosis of hepatocellular carcinoma.

CONCLUSIONS: This study analyzed the prognosis and function of HCC prognosis-related differential genes, predicted that the prognosis-related differential genes played an essential role in HCC immunity, and proposed therapeutic targets and biomarkers for HCC.

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