Immunogenic cell death-related gene markers mediating immune infiltration and poor prognosis in lung adenocarcinoma

赵伟军 胡锡麟 张纬 胡文涛

doi:10.16098/j.issn.0529-1356.2026.02.008

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Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (2) : 202-217. DOI: 10.16098/j.issn.0529-1356.2026.02.008

Cancer Biology

Immunogenic cell death-related gene markers mediating immune infiltration and poor prognosis in lung adenocarcinoma

ZHAO Wei-jun^*, HU Xi-lin, ZHANG Wei, HU Wen-tao

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Abstract

Objective To investigate the immunogenic cell death-related gene markers mediating immune infiltration and poor prognosis in lung adenocarcinoma. Methods Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we analysed the expression profile of immunogenic cell death (ICD) genes in lung adenocarcinoma (LUAD), screened for the set of differentially expressed ICD-related genes (ICD-RGs) by weighted gene co-expression network analysis (WGCNA), established the LASSO-Cox prognostic model and carried out the functional and drug sensitivity analysis; in vitro validation of the inhibitory effect of BI-2536 on the proliferation and migration of LUAD cells, and verification of the expression of ICD-RGs by Western blotting of three clinical samples. Results Differential genes of ICD-related subtypes were mainly enriched in aminoacyl-transfer RNA(tRNA) biosynthesis, citric acid cycle, base excision repair, oxidative phosphorylation, protein export, spliceosome, antigen processing and presentation, B-cell receptor signaling pathway, chemokine signaling pathway, cytokine-cytokine receptor interactions, natural killer cell-mediated cytotoxicity, and T-cell receptor signaling pathway, |NES|>1, P<0.05; ICD-RGs were significantly associated with both prognosis and immune microenvironment in LUAD patients (all P<0.05); BI-2536 had an inhibitory effect on the proliferation, invasion, and migration of both A549 and H1650 cells, P<0.05; Nomograms developed through the network calculator had a better predictive mechanism, and both receiver operating characteristic(ROC) and decision curve analysis(DCA) over time showed that nomograms were better predictors of prognosis; ICD-RGs showed differential expression in LUAD tissues and normal tissues in Human Protein Atlas(HPA) and Western blotting. Conclusion ICD-RGs are significantly associated with immunity and prognosis of LUAD, and BI-2536 can be used as a clinical drug to inhibit the growth migration and invasion of LUAD cells, mediate the ICD-RGs pathway and biofunctional activity. In addition, the newly developed nomogram provides a more convenient and accurate method to predict the overall survival of LUAD patients.

Key words

Lung adenocarcinoma

/ Immunogenic cell death / Immune infiltration / Poor prognosis / Immunohisto-chemistry / Western blotting / Human

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ZHAO Wei-jun, HU Xi-lin, ZHANG Wei, HU Wen-tao.

Immunogenic cell death-related gene markers mediating immune infiltration and poor prognosis in lung adenocarcinoma

[J]. Acta Anatomica Sinica. 2026, 57(2): 202-217 https://doi.org/10.16098/j.issn.0529-1356.2026.02.008

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