Characterization of immunogenic cell death regulators predicts survival and immunotherapy response in lung adenocarcinoma

Lung adenocarcinoma (LUAD) is highly lethal tumor; understanding immune response is crucial for current effective treatment. Research investigated immunogenic cell death (ICD) impact on LUAD through 75 ICD-related genes which encompass cell damage, endoplasmic reticulum stress, microenvironment, and...

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Published in:Life sciences (1973) 2024-02, Vol.338, p.122396-122396, Article 122396
Main Authors: Zhou, Desheng, Cui, Yachao, Zhu, Minggao, Lin, Yunen, Guo, Jing, Li, Yingchang, Zhang, Junwei, Wu, Zhenpeng, Guo, Jie, Chen, Yongzhen, Liang, Wendi, Lin, Weiqi, Lei, Kefan, Zhao, Ting, You, Qiang
Format: Article
Language:English
Subjects:
Adenocarcinoma of Lung - drug therapy
Adenocarcinoma of Lung - genetics
Endothelial Cells
Humans
Immunogenic Cell Death
Immunotherapy
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Tumor Microenvironment
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Summary:Lung adenocarcinoma (LUAD) is highly lethal tumor; understanding immune response is crucial for current effective treatment. Research investigated immunogenic cell death (ICD) impact on LUAD through 75 ICD-related genes which encompass cell damage, endoplasmic reticulum stress, microenvironment, and immunity. Transcriptome data and clinical info were analyzed, revealing two ICD-related clusters: B, an immune osmotic subgroup, had better prognosis, stronger immune signaling, and higher infiltration, while A represented an immune-deficient subgroup. Univariate Cox analysis identified six prognostic genes (AGER, CD69, CD83, CLEC9A, CTLA4, and NT5E), forming a validated risk score model. It was validated across datasets, showing predictive performance. High-risk group had unfavorable prognosis, lower immune infiltration, and higher chemotherapy sensitivity. Conversely, low-risk group had better prognosis, higher immune infiltration, and favorable immunotherapy response. The key gene NT5E was examined via immunohistochemistry, with higher expression linked to poorer prognosis. NT5E was predominantly expressed in B cells, fibroblasts, and endothelial cells, correlated with immune checkpoints. These outcomes suggest that NT5E can serve as a LUAD therapeutic target. The study highlights gene predictive value, offers an efficient tumor assessment tool, guides clinical treatment strategies, and identifies NT5E as therapeutic target for LUAD.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2023.122396