Zheng Yifan, Lin Yufeng, Zhang Yongcheng, Liu Shangjie, Yang Yongxia, Huang Wenbin
Department of Breast Care Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
College of Medical Information Engineering, Guangdong Pharmaceutical University, Guangzhou, China.
Transl Cancer Res. 2024 Nov 30;13(11):5815-5829. doi: 10.21037/tcr-24-513. Epub 2024 Nov 21.
Disulfidptosis is a novel form of cell death triggered by disulfide stress that may have important implications for breast cancer (BC) pathogenesis. Nevertheless, studies identifying disulfidptosis-associated long non-coding RNAs (lncRNAs) in BC have not been reported. This study aimed to investigate the prognostic potential of disulfidptosis-related lncRNAs in BC.
RNA-sequencing data and clinical information of BC patients were obtained from The Cancer Genome Atlas (TCGA) database. The lncRNAs associated with disulfidptosis were identified through co-expression analysis. Subsequently, a risk signature consisting of 10 lncRNAs was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses, and its predictive power was validated.
The risk signature was found to be an independent prognostic factor for BC patients. Notably, the two subgroups defined by the risk signature exhibited different mutant gene profiles, and risk scores were significantly correlated with tumor mutation burden (TMB). Additionally, single-sample gene set enrichment analysis (ssGSEA) and immune checkpoint analyses indicated that the predicted trait was significantly associated with the immune status of BC patients. Furthermore, 55 potential anticancer drugs were identified that were associated with the signature.
In this study, we successfully developed a prognostic model based on disulfidptosis-related lncRNAs, which enhances the accuracy of predicting the prognosis of BC patients. This model also offers a potential target and theoretical foundation for BC treatment, laying a robust groundwork for future research on the functional roles of disulfidptosis-associated lncRNAs in BC.
二硫化物诱导的细胞焦亡是一种由二硫键应激引发的新型细胞死亡形式，可能对乳腺癌（BC）的发病机制具有重要意义。然而，尚未有研究报道在BC中鉴定与二硫化物诱导的细胞焦亡相关的长链非编码RNA（lncRNA）。本研究旨在探讨BC中与二硫化物诱导的细胞焦亡相关lncRNA的预后潜力。
从癌症基因组图谱（TCGA）数据库中获取BC患者的RNA测序数据和临床信息。通过共表达分析鉴定与二硫化物诱导的细胞焦亡相关的lncRNA。随后，使用单变量Cox分析和最小绝对收缩和选择算子（LASSO）分析构建了一个由10个lncRNA组成的风险特征，并验证了其预测能力。
发现该风险特征是BC患者的独立预后因素。值得注意的是，由该风险特征定义的两个亚组表现出不同的突变基因谱，并且风险评分与肿瘤突变负荷（TMB）显著相关。此外，单样本基因集富集分析（ssGSEA）和免疫检查点分析表明，预测特征与BC患者的免疫状态显著相关。此外，还鉴定出55种与该特征相关的潜在抗癌药物。
在本研究中，我们成功开发了一种基于二硫化物诱导的细胞焦亡相关lncRNA的预后模型，提高了预测BC患者预后的准确性。该模型还为BC治疗提供了潜在靶点和理论基础，为未来研究二硫化物诱导的细胞焦亡相关lncRNA在BC中的功能作用奠定了坚实基础。
