Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu Province, 211166, PR China.
Comput Biol Med. 2024 Feb;169:107930. doi: 10.1016/j.compbiomed.2024.107930. Epub 2024 Jan 4.
Hepatocellular carcinoma (HCC) is associated with a high mortality rate, where resistance to immunotherapy and chemotherapy plays a crucial role. A newly identified form of cell death called disulfidptosis shows promise, but its biological mechanism in HCC remains uncertain. In this study, a prognostic model was developed for Disulfidptosis-related long non-coding RNAs (DRLs) from 370 HCC patients sourced from TCGA-LIHC, utilizing five key features: AC026356.1, AC073254.1, PXN-AS1 expression, AC026412.3, and AC099066.2. High-risk HCC patients had lower survival, CD4 T cell infiltration, and elevated immune checkpoint gene expression. Furthermore, based on the features of DRLs, HCC was classified into three subtypes. Notably, patients belonging to different subtypes demonstrated varying overall survival rates, immune cell infiltration patterns, and sensitivity to immune therapy. Moreover, the novel DRL AC026412.3 (HR = 40.207) emerged as the most significant prognostic factor, exhibiting high expression across all HCC cells. Elevated expression of AC026412.3 promoted HCC cell proliferation and induced resistance to gefitinib. In conclusion, we have discovered five DRLs and constructed a prognostic risk model. Our findings validate the correlation between DRL-related prognostic models, tumor subtypes, and the HCC immune microenvironment along with its implications for immunotherapy. Moreover, further investigation into the molecular mechanisms of key biomarkers like AC026412.3 in the future will contribute significantly to advancing our comprehension of HCC's pathogenesis and drug resistance mechanisms.
肝细胞癌 (HCC) 死亡率高,其对免疫治疗和化疗的耐药性起着至关重要的作用。一种新发现的细胞死亡形式——二硫键细胞死亡 (Disulfidptosis) 显示出了希望,但它在 HCC 中的生物学机制尚不清楚。在这项研究中,我们利用来自 TCGA-LIHC 的 370 名 HCC 患者的数据,开发了一个与二硫键细胞死亡相关的长非编码 RNA (DRLs) 的预后模型,使用了五个关键特征:AC026356.1、AC073254.1、PXN-AS1 表达、AC026412.3 和 AC099066.2。高风险 HCC 患者的生存率较低,CD4 T 细胞浸润水平较低,免疫检查点基因表达水平较高。此外,基于 DRLs 的特征,我们将 HCC 分为三种亚型。值得注意的是,不同亚型的患者表现出不同的总生存率、免疫细胞浸润模式和对免疫治疗的敏感性。此外,新型 DRL AC026412.3(HR=40.207)是最重要的预后因素,在所有 HCC 细胞中均呈高表达。AC026412.3 的表达升高促进了 HCC 细胞的增殖,并诱导了对吉非替尼的耐药性。总之,我们发现了五个 DRLs,并构建了一个预后风险模型。我们的研究结果验证了 DRL 相关预后模型、肿瘤亚型与 HCC 免疫微环境之间的相关性,以及它们对免疫治疗的影响。此外,未来对关键生物标志物如 AC026412.3 的分子机制的进一步研究,将对深入了解 HCC 的发病机制和耐药机制有重要贡献。