Zhang Tianze, Chen Yuqing, Xiang Zhiping
Department of Gastrointestinal Surgery, The Second Hospital of Shandong University, Jinan, China.
Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, China.
Artif Cells Nanomed Biotechnol. 2025 Dec;53(1):1-13. doi: 10.1080/21691401.2024.2440415. Epub 2024 Dec 19.
Gastric cancer remains one of the deadliest cancers globally due to delayed detection and limited treatment options, underscoring the critical need for innovative prognostic methods. Disulfidptosis, a recently discovered programmed cell death triggered by disulphide stress, presents a fresh avenue for therapeutic exploration. This research examines disulfidptosis-related long noncoding RNAs (DRLs) in gastric cancer, with the goal of leveraging these lncRNAs as potential markers to enhance patient outcomes and treatment approaches. Comprehensive genomic and clinical data from stomach adenocarcinoma (STAD) were obtained from The Cancer Genome Atlas (TCGA). Employing least absolute shrinkage and selection operator (LASSO) regression analysis, a prognostic model was devised incorporating five key DRLs to forecast survival rates. The effectiveness of this model was validated using Kaplan-Meier survival plots, receiver operating characteristic (ROC) curves, and extensive functional enrichment studies. The importance of select lncRNAs and the expression variability of genes tied to disulfidptosis were validated via quantitative real-time PCR (qRT-PCR) and Western blot tests, establishing a solid foundation for their prognostic utility. Analyses of functional enrichment and tumour mutation burden highlighted the biological importance of these DRLs, connecting them to critical cancer pathways and immune responses. These discoveries broaden our comprehension of the molecular framework of gastric cancer and bolster the development of tailored treatment plans, highlighting the substantial role of DRLs in clinical prognosis and therapeutic intervention.
由于检测延迟和治疗选择有限，胃癌仍然是全球最致命的癌症之一，这凸显了对创新预后方法的迫切需求。二硫化物诱导的细胞焦亡是一种最近发现的由二硫键应激引发的程序性细胞死亡，为治疗探索提供了新途径。本研究调查了胃癌中与二硫化物诱导的细胞焦亡相关的长链非编码RNA（DRL），目的是利用这些长链非编码RNA作为潜在标志物，以改善患者预后和治疗方法。从癌症基因组图谱（TCGA）获得了胃腺癌（STAD）的综合基因组和临床数据。采用最小绝对收缩和选择算子（LASSO）回归分析，设计了一个包含五个关键DRL的预后模型来预测生存率。使用Kaplan-Meier生存曲线、受试者工作特征（ROC）曲线和广泛的功能富集研究验证了该模型的有效性。通过定量实时PCR（qRT-PCR）和蛋白质印迹试验验证了所选长链非编码RNA的重要性以及与二硫化物诱导的细胞焦亡相关基因的表达变异性，为它们的预后效用奠定了坚实基础。功能富集分析和肿瘤突变负担分析突出了这些DRL的生物学重要性，将它们与关键的癌症途径和免疫反应联系起来。这些发现拓宽了我们对胃癌分子框架的理解，并促进了量身定制治疗方案的开发，突出了DRL在临床预后和治疗干预中的重要作用。
