Evidence map›Paper›PMID 39945555›Full record

ArticleCancer medicine2025

Molecular Subtyping and Therapeutic Targeting of IFNG-Driven Immunogenic Cell Death in Lung Adenocarcinoma.

Lifeng Li, Yaqi Yang, Mengle Peng, Biyue Wang, Lili Zhu, Chengxin Chen, Zhirui Fan, Xiaoran Duan, Ruyue Xue, Xuefeng Lv and 2 more

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In one paragraph

Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Lifeng LiNational Engineering Laboratory for Internet Medical Systems and Applications, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Yaqi YangNational Engineering Laboratory for Internet Medical Systems and Applications, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Mengle PengDepartment of Clinical Laboratory, Henan No. 3 Provincial People's Hospital, Zhengzhou, Henan, China.ORCID https://orcid.org/0000-0001-8693-6923
Biyue WangDepartment of Nephrology, Seventh People's Hospital of Zhengzhou, Zhengzhou, Henan, China.
Lili ZhuNational Engineering Laboratory for Internet Medical Systems and Applications, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Chengxin ChenNational Engineering Laboratory for Internet Medical Systems and Applications, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Zhirui FanDepartment of Integrated Traditional and Western Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Xiaoran DuanNational Engineering Laboratory for Internet Medical Systems and Applications, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Ruyue XueNational Engineering Laboratory for Internet Medical Systems and Applications, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Xuefeng LvDepartment of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Ming ChengDepartment of Medical Information, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Jie ZhaoNational Engineering Laboratory for Internet Medical Systems and Applications, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.ORCID https://orcid.org/0000-0003-1168-8384

Funding

Funding for Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University ZYCXTD2023005Henan Key Laboratory of Chronic Disease Management HMKF202103Key scientific research project plan of colleges and universities in Henan Province 22A416012National Science Foundation of China 32370976State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia Fund SKL-HIDCA-2022- JZ5Wu Jieping Medical Foundation Special Fund for Targeted Cancer Research 320.6750.2023-02-1
6 · The paper itself

Abstract

backgroundImmunogenic cell death (ICD) can be triggered by various therapies to induce anti-tumor immune responses, significantly enhancing treatment effectiveness, and is widely utilized in tumor immunotherapy.

methodsLUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) validated ICD-related molecular subtypes via consensus clustering. Clinical features, ICD genes, driver genes, mutations, tumor microenvironment, immune checkpoints, and drug sensitivity were compared. RT-qPCR, Western blot, immunofluorescence, ELISA, flow cytometry, and tube formation assays validated findings.

resultsDifferential expression of 33 ICD genes was observed between tumor and normal tissues. These genes were clustered into two groups via consensus clustering and validated with GEO data. Prognostic analysis indicated superior outcomes in cluster 2 across TCGA and GEO cohorts. Significant disparities in clinicopathological characteristics like stage, gender, and age were noted between subtypes. Cluster 2 exhibited heightened expression of ICD-related genes, driver genes, immune checkpoints, and immune cells. Cluster 2 also showed increased sensitivity to chemotherapy drugs. IFNG overexpression in A549 and H1299 cells induced CRT exposure, HMGB1 release, and ATP secretion, thereby promoting dendritic cell maturation and enhancing CD8+ T cell function. Additionally, IFNG boosted tumor angiogenesis via HMGB1 pathways, which could be mitigated by HMGB1 inhibition.

conclusionIdentification of novel ICD-related molecular subtypes holds promise for guiding personalized therapies, assessing prognosis, and predicting immunotherapy efficacy in LUAD. IFNG emerges as a potential prognostic biomarker and therapeutic target, influencing both the tumor microenvironment and angiogenesis. These findings offer new insights into therapeutic strategies targeting IFNG-mediated pathways in LUAD.

Indexed as

Adenocarcinoma of LungImmunogenic Cell DeathInterferon-gammaLung NeoplasmsBiomarkers, TumorCell Line, TumorFemaleGene Expression Regulation, NeoplasticHMGB1 ProteinHumansMaleMiddle AgedPrognosisTumor MicroenvironmentBiomarkers, TumorHMGB1 ProteinHMGB1 protein, humanIFNG protein, humanInterferon-gammaIFNGimmunogenic cell deathlung adenocarcinomamolecular subtypestumor microenvironment

Identifiers

PMID39945555
PMCPMC11822994

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.