乙型肝炎病毒相关肝细胞癌癌组织ARHGAP18水平及其基因调控网络分析

ARHGAP18 gene levels and its roles in gene regulation network in patients with hepatitis B virus-associated hepatocellular carcinoma

目的 探讨Rho GTP酶激活蛋白18(ARHGAP18)基因在乙型肝炎病毒相关肝细胞癌(HBV-HCC)组织水平变化及其功能。方法 在基因表达数据库(GEO)中下载数据集以评估ARHGAP18水平。应用UALCAN网站研究不同临床和病理特征的HCC组织ARHGAP18水平差异及其对预后的影响。在GEO数据集对HBV-HCC多组学队列转录组数据和甲基化阵列数据分析与ARHGAP18水平相关的表观遗传模式。结果 HBV感染患者肝组织ARHGAP18水平为(5.62±0.66),显著高于正常肝组织【(5.04±0.21),P<0.05】;HBV-HCC肿瘤组织ARHGAP18水平为(3988.63±1701.17),显著高于HBV-HCC癌旁肝组织【(1976.34±531.32),P<0.05】;在肝脏边缘组织、距肿瘤2~3 cm癌旁肝组织、肿瘤边缘癌旁肝组织、肿瘤外围组织和肿瘤中心组织ARHGAP18水平分别为(7.06±0.61)、(6.83±0.47)、(6.82±0.42)、(7.75±0.56)和(8.38±0.79),提示越向肿瘤中心组织,ARHGAP18水平呈异常升高趋势(P<0.05);ARHGAP18高水平的HCC患者生存期显著缩短(P<0.05);转录组数据提示ARHGAP18高水平组存在炎症反应、先天性免疫反应、适应性免疫反应和免疫调节等免疫炎症相关通路的激活。结论 ARHGAP18与HBV-HCC发生发展密切相关,其机制值得进一步研究。

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.