Abstract: Objective The purpose of this study was to investigate the Rho GTPase-activating protein 18 (ARHGAP18) gene levels and its roles in gene regulation network in patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). Methods In this study,4 datasets downloaded from the Gene Expression Omnibus (GEO) database was applied to evaluate the changes of ARHGAP18 gene levels. The ARHGAP18 levels in different clinic-pathological characteristics and its correlation to the prognosis of patients with HCC was analyzed in UALCAN website. The transcriptomic data and methylation array data from GEO dataset “HBV-HCC multi-omics cohort” were used to analyze the epigenetic patterns associated with ARHGAP18. Results The ARHGAP18 level in liver tissues from patients with chronic hepatitis B was (5.62±0.66), significantly higher than [(5.04±0.21),P<0.05] in normal control; the ARHGAP18 level in cancerous tissues from patients with HBV-HCC was (3988.63±1701.17), significantly higher than [(1976.34±531.32), P<0.05] in paranon-cancerous samples; the ARHGAP18 levels in liver margin, 2 to 3 cm liver tissue from the tumor, peritumor liver tissue, peri-tumor cancerous tissue and the center of tumors were(7.06±0.61), (6.83±0.47), (6.82±0.42), (7.75± 0.56) and (8.38 ± 0.79), suggesting a tendency of gradually increased ARHGAP18 levels from the so-called normal liver to the center of tumor(P<0.05); the high ARHGAP18 level was associated with shorter survival in patients with HCC (P<0.05); the transcriptomic data analysis found the aberrant activation of multiple immune and inflammation-related pathways, such as the inflammatory response, innate immune response, regulation of immune effector processes, and adaptive immune response in cancerous tissues with increased ARHGAP18 levels. Conclusion The ARHGAP18 might be involved in the hapatocarcinogenesis, and its mechanism deserves further study.

Key words: Hepatoma, ARHGAP18, Cellular senescence, Transcriptome, Gene Expression Omnibus