Chen Xi, Yang Chen
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Curr Med Chem. 2024 Apr 17. doi: 10.2174/0109298673294711240405090150.
Breast cancer (BRCA) is one of the leading causes of cancer-related death in women. The improvement of the BRCA risk assessment method is of positive clinical significance. Although many clues showed the potential role of disulfidptosis in BRCA as a novel type of programmed cell death, whether disulfidptosis is involved in BRCA tumorigenesis remains unclear.
We used LASSO-univariate Cox analysis and multivariate Cox analysis to identify six disulfidptosis-related lncRNAs (DPLs) that correlated with BRCA clinical outcome and confirmed that these DPLs were independent prognostic factors for BRCA (YTHDF3-AS1, AC002398.1, AL451085.2, AC092718.4, AC097662.1 and AC053503.5). The BRCA risk prognosis model was subsequently established based on these DPLs.
After verifying the model reliability in predicting prognosis, immune infiltration and somatic mutation analysis showed significant differences in the immune microenvironment and mutation of DPLs by risk stratification. Immunotherapy response and drug resistance analysis suggest the reference value of DPLs in clinical individualized therapy.
The abnormal expressions of selected DPLs were further validated by the BRCA cell line experiment. Our results shed new light on the role of DPLs in BRCA.
乳腺癌（BRCA）是女性癌症相关死亡的主要原因之一。改进BRCA风险评估方法具有积极的临床意义。尽管许多线索表明二硫键介导的程序性坏死作为一种新型程序性细胞死亡在BRCA中具有潜在作用，但二硫键介导的程序性坏死是否参与BRCA肿瘤发生仍不清楚。
我们使用LASSO单变量Cox分析和多变量Cox分析来鉴定与BRCA临床结局相关的6个二硫键介导的程序性坏死相关lncRNA（DPL），并证实这些DPL是BRCA的独立预后因素（YTHDF3-AS1、AC002398.1、AL451085.2、AC092718.4、AC097662.1和AC053503.5）。随后基于这些DPL建立了BRCA风险预后模型。
在验证模型预测预后的可靠性后，免疫浸润和体细胞突变分析显示，按风险分层，DPL在免疫微环境和突变方面存在显著差异。免疫治疗反应和耐药性分析表明DPL在临床个体化治疗中的参考价值。
BRCA细胞系实验进一步验证了所选DPL的异常表达。我们的结果为DPL在BRCA中的作用提供了新的见解。
