PDF(Pubmed)
Abstract：
Disulfidptosis, a newly identified mode of programmed cell death, is yet to be comprehensively elucidated with respect to its multi-omics characteristics in tumors, specific pathogenic mechanisms, and antitumor functions in liver cancer. This study included 10,327 tumor and normal tissue samples from 33 cancer types. In-depth analyses using various bioinformatics tools revealed widespread dysregulation of disulfidptosis-related genes (DRGs) in pan-cancer and significant associations with prognosis, genetic variations, tumor stemness, methylation levels, and drug sensitivity. Univariate and multivariate Cox regression and LASSO regression were used to screen and construct prognosis-related hub DRGs and predictive models in the context of liver cancer. Subsequently, single cell analysis was conducted to investigate the subcellular localization of RPN1, a hub DRG, in various solid tumors. Western blotting was performed to validate the expression of RPN1 at both cellular and tissue levels. Additionally, functional experiments, including CCK8, EdU, clone, and transwell assays, indicated that RPN1 knockdown promoted the proliferative and invasive capacities of liver cancer cells. Therefore, this study elucidated the multi-omics characteristics of DRGs in pan-cancer and established a prognostic model for liver cancer. Additionally, this study revealed the molecular functions of RPN1 in liver cancer, suggesting its potential as a therapeutic target for this disease.
摘要：
二硫化物下垂，一种新发现的程序性细胞死亡模式，关于其在肿瘤中的多组学特征，还有待全面阐明，特定的致病机制，和肝癌的抗肿瘤功能。这项研究包括来自33种癌症类型的10,327个肿瘤和正常组织样本。使用各种生物信息学工具进行的深入分析揭示了泛癌症中二硫键凋亡相关基因（DRGs）的广泛失调以及与预后的显着关联。遗传变异,肿瘤干性，甲基化水平，和药物敏感性。单变量和多变量Cox回归和LASSO回归用于筛选和构建肝癌背景下的预后相关枢纽DRGs和预测模型。随后，进行单细胞分析以研究RPN1的亚细胞定位，在各种实体瘤中。进行Western印迹以验证RPN1在细胞和组织水平上的表达。此外,功能实验，包括CCK8，EdU，克隆人,和transwell分析，表明RPN1敲低促进了肝癌细胞的增殖和侵袭能力。因此,这项研究阐明了泛癌症中DRGs的多组学特征，并建立了肝癌的预后模型。此外,这项研究揭示了RPN1在肝癌中的分子功能，表明其作为这种疾病治疗靶点的潜力。
