PDF(Pubmed)
Abstract：
Disulfidptosis, a novel form of regulated cell death (RCD) associated with metabolism, represents a promising intervention target in cancer therapy. While abnormal lncRNA expression is associated with colon cancer development, the prognostic potential and biological characteristics of disulfidptosis-related lncRNAs (DRLs) remain unclear. Consequently, the research aimed to discover a novel indication of DRLs with significant prognostic implications, and to investigate their possible molecular role in the advancement of colon cancer. Here, we acquired RNA-seq data, pertinent clinical data, and genomic mutations of colon adenocarcinoma (COAD) from the TCGA database, and then DRLs were determined through Pearson correlation analysis. A total of 434 COAD patients were divided in to three subgroups through clustering analysis based on DRLs. By utilizing univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) algorithm, and multivariate Cox regression analysis, we ultimately created a prognostic model consisting of four DRLs (AC007728.3, AP003555.1, ATP2B1.AS1, and NSMCE1.DT), and an external database was used to validate the prognostic features of the risk model. According to the Kaplan-Meier curve analysis, patients in the low-risk group exhibited a considerably superior survival time in comparison to those in the high-risk group. Enrichment analysis revealed a significant association between metabolic processes and the genes that were differentially expressed in the high- and low-risk groups. Additionally, significant differences in the tumor immune microenvironment landscape were observed, specifically pertaining to immune cells, function, and checkpoints. High-risk patients exhibited a low likelihood of immune evasion, as indicated by the Tumor Immune Dysfunction and Exclusion (TIDE) analysis. Patients who exhibit both a high risk and high Tumor Mutational Burden (TMB) experience the least amount of time for survival, whereas those belonging to the low-risk and low-TMB category demonstrate the most favorable prognosis. In addition, the risk groups determined by the 4-DRLs signature displayed distinct drug sensitivities. Finally, we confirmed the levels of expression for four DRLs through rt-qPCR in both tissue samples from colon cancer patients and cell lines. Taken together, the first 4-DRLs-based signature we proposed may serve for a hopeful instrument for forecasting the prognosis, immune landscape, and therapeutic responses in colon cancer patients, thereby facilitating optimal clinical decision-making.
摘要：
二硫化物下垂，一种与代谢相关的新型调节细胞死亡（RCD），代表了癌症治疗中一个有希望的干预目标。虽然lncRNA的异常表达与结肠癌的发展有关，目前尚不清楚二硫键凋亡相关lncRNAs(DRLs)的预后潜力和生物学特征.因此,这项研究旨在发现一种具有重大预后意义的DRLs的新适应症，并研究它们在结肠癌进展中可能的分子作用。这里,我们获得了RNA-seq数据,相关临床数据，和来自TCGA数据库的结肠腺癌（COAD）的基因组突变，然后通过Pearson相关分析确定DRL。通过基于DRL的聚类分析，将434例COAD患者分为三个亚组。通过利用单变量Cox回归，最小绝对收缩和选择算子(LASSO)算法，和多变量Cox回归分析，我们最终创建了由4个DRL组成的预后模型(AC007728.3,AP003555.1,ATP2B1.AS1和NSMCE1。DT),并使用外部数据库验证风险模型的预后特征。根据Kaplan-Meier曲线分析,与高危组相比,低危组患者的生存时间显著延长.富集分析显示，代谢过程与高风险和低风险组中差异表达的基因之间存在显着关联。此外,观察到肿瘤免疫微环境景观的显著差异，特别是与免疫细胞有关的，函数,和检查站。高风险患者表现出免疫逃避的可能性很低，如肿瘤免疫功能障碍和排斥（TIDE）分析所示。同时表现出高风险和高肿瘤突变负担（TMB）的患者生存时间最少，而属于低风险和低TMB类别的患者显示出最有利的预后。此外,由4-DRLs特征确定的风险组显示出不同的药物敏感性.最后,我们通过rt-qPCR证实了4种DRL在结肠癌患者和细胞系中的表达水平.一起来看,我们提出的第一个基于4-DRL的签名可能会成为预测预后的有希望的工具，免疫景观，和结肠癌患者的治疗反应，从而促进最佳的临床决策。
