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ABSTRACT
Immunogenic cell death (ICD) has been increasingly indicated to be related to caners. However, ICD’s role in Lung adenocarcinoma (LUAD) is still not well investigated. Clinical data along with associated mRNA expression profiles from LUAD cases were collected in TCGA and GEO databases. 13 ICD-related genes were identified. Relations of ICD-related genes expression with prognosis of patients, tumor immune microenvironment (TIME) was analyzed. Then, candidate genes were identified and the prognostic signature were constructed. Afterwards, one nomogram incorporating those chosen clinical data together with risk scores were built. Finally, the effect of HSP90AA1, one gene of the prognostic signature, on LUAD cell were analyzed. Two clusters were identified, which were designated as the ICD-high or -low subtype according to ICD-related genes levels. ICD-high subgroup showed good prognosis, high immune cell infiltration degrees, and enhanced immune response signaling activity compared with ICD-low subtype. Moreover, we established and verified the risk signature based on ICD-related genes. High risk group predicted poor prognosis of LUAD independently and presented negative association with immune score and immune status. Furthermore, nomogram contributed to the accurate prediction of LUAD prognostic outcome. Finally, HSP90AA1 levels were remarkably elevated within tumor cells in comparison with healthy pulmonary epithelial cells. HSP90α, HSP90AA1 protein product, promoted growth, migration, and invasion of LUAD cells. Molecular subtypes and prognostic model were identified by incorporating ICD-related genes, and it was related to TIME and might be adopted for the accurate prediction of LUAD prognosis.
Abbreviation
| GAPDH | = | Glyceraldehyde Phosphate Dehydrogenase |
| CCK-8 | = | Cell Counting Kit-8 |
| RT-qPCR | = | Real-Time Quantitative Polymerase Chain Reaction |
| HMGB1 | = | High Mobility Group Box 1 |
| FASLG | = | Factor Related Apoptosis Ligand |
| PDIA3 | = | Protein Disulfide Isomerase A3 |
| ANXA1 | = | Annexin-A1 |
| HSP90AA1 | = | Heat shock protein HSP 90α |
| IFNG | = | Interferon γ |
| TLR4 | = | Toll-Like Receptor 4 |
| CXCL10 | = | C-X-C Motif Chemokine Ligand 10 |
| CASP8 | = | caspase 8 |
| BAX | = | Bcl2 Associated X Protein |
| P2RX7 | = | Purinergic Receptor P2X |
| LGIC7 | = | Ligand Gated Ion Channel 7 |
| TNF | = | Tumor Necrosing Factor |
| CCL2 | = | Chemokine Ligand 2 |
| ATP | = | Adenosine-Triphosphate |
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
Yinying Dong and Haijun Lu contributed to study conception, manuscript reviewing, and supervising. Hao Song, Mingjin Xu, Jian Liu were responsible for collecting and analyzing data. Xiao Yu, Qingfeng Chen, Xiangyin Sun and Qiuxiao Wang were in charge of manuscript drafting, table and figure drawing. Bin Zheng, Xiaomeng Ji and Ruimei Ren performed experiments. The authors agreed the final version for publication.
Data availability statement
All data utilized in this work can be acquired from corresponding authors on request.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2023.2300591.