三阴性乳腺癌中与二硫化物依赖性细胞焦亡相关簇的鉴定及二硫化物依赖性细胞焦亡相关基因预后特征的构建

Identification of disulfidptosis-related clusters and construction of a disulfidptosis-related gene prognostic signature in triple-negative breast cancer.

作者信息

Wu Jie, Cai Yan, Zhao Gaiping

机构信息

Key Laboratory of Hydrodynamics (Ministry of Education), School of Ocean and Civil Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.

出版信息

Heliyon. 2024 Jun 14;10(12):e33092. doi: 10.1016/j.heliyon.2024.e33092. eCollection 2024 Jun 30.

Abstract

OBJECTIVE

This study aimed to explore disulfidptosis-related clusters of triple-negative breast cancer (TNBC) and build a reliable disulfidptosis-related gene signature for forecasting TNBC prognosis.

METHODS

The disulfidptosis-related clusters of TNBC were identified based on public datasets, and a comparative analysis was conducted to assess their differences in the overall survival (OS) and immune cell infiltration. Morever, the differentially expressed genes (DEGs) between clusters were recognized. Then, the prognostic DEGs were then chosen. A prognostic signature was constructed by the prognostic DEGs, followed by nomogram construction, drug sensitivity, immune correlation, immunotherapy response prediction, and cluster association analyses.

RESULTS

Two disulfidptosis-related clusters of TNBC were identified, which had different OS and macrophage infiltration. Moreover, 235 DEGs were identified between two clusters. A prognostic signature was then constructed by five prognostic DEGs including HLA-DQA2, CCL13, GBP1, LAMP3, and SLC7A11. This signature was highly valuable in predicting prognosis. A nomogram was built by risk score and AJCC stage, which could forecast OS accurately. Moreover, patients with high-risk scores exhibited greater sensitivity to chemotherapy drugs such as lapatinib and had a lower immunotherapy response.

CONCLUSIONS

Two TNBC clusters linked to disulfidptosis were identified, with different OS and immune cell infiltration. Moreover, a five-disulfidptosis-related gene signature may be a powerful prognostic biomarker for TNBC.

摘要

目的

本研究旨在探索三阴性乳腺癌(TNBC)中与二硫化物诱导细胞程序性坏死相关的簇,并构建一个可靠的与二硫化物诱导细胞程序性坏死相关的基因特征,用于预测TNBC的预后。

方法

基于公开数据集鉴定TNBC中与二硫化物诱导细胞程序性坏死相关的簇,并进行比较分析,以评估它们在总生存期(OS)和免疫细胞浸润方面的差异。此外,识别簇之间的差异表达基因(DEG)。然后选择预后DEG。由预后DEG构建预后特征,随后进行列线图构建、药物敏感性、免疫相关性、免疫治疗反应预测和簇关联分析。

结果

鉴定出TNBC的两个与二硫化物诱导细胞程序性坏死相关的簇,它们具有不同的OS和巨噬细胞浸润。此外,在两个簇之间鉴定出235个DEG。然后由包括HLA-DQA2、CCL13、GBP1、LAMP3和SLC7A11在内的五个预后DEG构建预后特征。该特征在预测预后方面具有很高的价值。通过风险评分和美国癌症联合委员会(AJCC)分期构建列线图,可准确预测OS。此外,高风险评分的患者对拉帕替尼等化疗药物表现出更高的敏感性,且免疫治疗反应较低。

结论

鉴定出与二硫化物诱导细胞程序性坏死相关的两个TNBC簇,它们具有不同的OS和免疫细胞浸润。此外,一个与二硫化物诱导细胞程序性坏死相关的五基因特征可能是TNBC的一个强大的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/11238051/92e169eaf8ee/gr1.jpg

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