背景:肝细胞癌是最常见的恶性肿瘤之一,无法准确预测其预后和治疗结果。ADP-核糖基化(ADPR)是涉及蛋白质运输和免疫应答的蛋白质的翻译后修饰。因此,有必要探讨与肝细胞癌治疗预后和疗效相关的ADPR相关基因。
方法:我们下载了肝细胞癌样本的数据,以鉴定ADPR相关基因作为预后标志物,并基于单变量和多变量COX回归分析建立了新的ADPR相关指数(ADPRI)。患者预后,临床特征,体细胞变异,肿瘤免疫微环境,系统分析化疗反应和免疫治疗反应。最后,初步探讨了ARFIP2在肝癌细胞中的作用。
结果:由四个ADPR相关基因组成的ADPRI(ARL8B,ARFIP2,PARP12,ADPRHL1)被确定为肝细胞癌患者生存的可靠预测因子,并使用外部数据集进行了验证。与低ADPRI组相比,高ADPRI组的突变频率较高,高ADPRI组的免疫浸润和患者从免疫检查点抑制剂治疗中获益更多.此外,我们预测一些天然小分子药物是肝细胞癌的潜在治疗靶点。最后,敲除ARFIP2通过诱导肝癌细胞G1/S期细胞周期阻滞抑制肝癌细胞的增殖和迁移。
结论:ADPRI可以准确预测肝细胞癌患者的预后和免疫治疗反应,为今后肝细胞癌患者的精准治疗提供有价值的见解。
Hepatocellular carcinoma is one of the most common malignancies, and its prognosis and treatment outcome cannot be accurately predicted. ADP-ribosylation (ADPR) is a post-translationa modification of proteins involved in protein trafficking and immune response. Therefore, it is necessary to explore the ADPR-related genes associated with the prognosis and therapeutic efficacy of hepatocellular carcinoma treatments.
We downloaded the data of hepatocellular carcinoma samples to identify ADPR-related genes as prognostic markers, and established a novel ADPR-related index (ADPRI) based on univariate and multivariate COX regression analyses. Patients\' prognosis, clinical features, somatic variant, tumor immune microenvironment, chemotherapeutic response and immunotherapeutic response were systematically analyzed. Finally, the role of ARFIP2 in hepatocellular carcinoma cells was preliminarily explored in vitro.
The ADPRI consisting of four ADPR related genes (ARL8B, ARFIP2, PARP12, ADPRHL1) was established to be a reliable predictor of survival in patients with hepatocellular carcinoma and was validated using external datasets. Compared with the low ADPRI group, the high ADPRI group presented higher levels of mutation frequency, immune infiltration and patients in high ADPRI group benefit more from immune checkpoint inhibitor treatment. In addition, we predicted some natural small molecule drugs as potential therapeutic targets for hepatocellular carcinoma. Finally, Knockdown of ARFIP2 inhibits the proliferation and migration of hepatocellular carcinoma cells by inducing the G1/S phase cell cycle arrest in HCC cells.
The ADPRI can be used to accurately predict the prognosis and immunotherapeutic response of hepatocellular carcinoma patients and providing valuable insights for future precision treatment of patients with hepatocellular carcinoma.