Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China.
J Cancer Res Clin Oncol. 2023 Oct;149(13):12145-12164. doi: 10.1007/s00432-023-05109-y. Epub 2023 Jul 10.
Immunotherapy, represented by immune checkpoint inhibitors, has made significant progress in the treatment of cancer. Numerous studies have demonstrated that antitumor therapies targeting cell death exhibit synergistic effects with immunotherapy. Disulfidptosis is a recently discovered form of cell death, and its potential influence on immunotherapy, similar to other regulated cell death processes, requires further investigation. The prognostic value of disulfidptosis in breast cancer and its role in the immune microenvironment has not been investigated.
High dimensional weighted gene coexpression network analysis (hdWGCNA) and Weighted co-expression network analysis (WGCNA) methods were employed to integrate breast cancer single-cell sequencing data and bulk RNA data. These analyses aimed to identify genes associated with disulfidptosis in breast cancer. Risk assessment signature was constructed using Univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses.
In this study, we constructed a risk signature by disulfidptosis-related genes to predict overall survival and immunotherapy response in BRCA patients. The risk signature demonstrated robust prognostic power and accurately predicted survival compared to traditional clinicopathological features. It also effectively predicted the response to immunotherapy in patients with breast cancer. Through cell communication analysis in additional single-cell sequencing data, we identified TNFRSF14 as a key regulatory gene. Combining TNFRSF14 targeting and immune checkpoint inhibition to induce disulfidptosis in tumor cells could potentially suppress tumor proliferation and enhance survival in patients with BRCA.
免疫疗法，以免疫检查点抑制剂为代表，在癌症治疗方面取得了重大进展。大量研究表明，针对细胞死亡的抗肿瘤疗法与免疫疗法具有协同作用。二硫键细胞死亡是一种新发现的细胞死亡形式，其对免疫疗法的潜在影响类似于其他调控细胞死亡过程，需要进一步研究。二硫键细胞死亡在乳腺癌中的预后价值及其在免疫微环境中的作用尚未得到研究。
采用高维加权基因共表达网络分析（hdWGCNA）和加权共表达网络分析（WGCNA）方法整合乳腺癌单细胞测序数据和批量 RNA 数据。这些分析旨在鉴定与乳腺癌中二硫键细胞死亡相关的基因。使用单变量 Cox 和最小绝对值收缩和选择算子（LASSO）分析构建风险评估签名。
本研究构建了一个基于二硫键细胞死亡相关基因的风险签名，用于预测 BRCA 患者的总生存期和免疫治疗反应。该风险签名表现出强大的预后能力，与传统的临床病理特征相比，能够更准确地预测生存情况。它还能有效地预测乳腺癌患者对免疫治疗的反应。通过对额外的单细胞测序数据中的细胞通讯分析，我们确定 TNFRSF14 是一个关键的调节基因。结合 TNFRSF14 靶向和免疫检查点抑制诱导肿瘤细胞中二硫键细胞死亡，可能抑制肿瘤增殖并提高 BRCA 患者的生存率。
