Evidence map›Paper›PMID 41501264›Full record

ArticleCell biology and toxicology2026

Harnessing machine learning-driven multiomics integration: deciphering programmed cell death networks for prognostication and immunotherapy prediction in lung adenocarcinoma.

Wuguang Chang, Bin Luo, Zhesheng Wen, Youfang Chen

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Article in Cell biology and toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Wuguang Chang *Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Bin Luo *Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Zhesheng WenDepartment of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. wenzhsh@sysucc.org.cn.
Youfang ChenDepartment of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. chenyouf@sysucc.org.cn.

Funding

Fostering Program for NSFC Young Applicants (Tulip Talent Training Program) of Sun Yat-sen University Cancer Center 2024yfd11Guangdong Basic and Applied Basic Research Foundation 2024A1515013219
6 · The paper itself

Abstract

backgroundProgrammed cell death (PCD) patterns play important roles in lung adenocarcinoma (LUAD) development as well as treatment resistance, and in-depth study of PCD is beneficial for improving the therapeutic paradigm for LUAD.

methodsFourteen PCD-related patterns were integrated and multiple datasets from TCGA and GEO were collected to develop a PCD signature using 101 machine learning algorithm combinations. Prognosis, immune cell infiltration, and sensitivity to chemotherapy and immunotherapy were compared between different risk groups and validated by multiple bulk RNA-seq and scRNA-seq datasets of patients receiving immunotherapy. CellChat was used to analyze the cellular interactions between patients with different PCD groups. Immune cell infiltration in the tumor tissues of 38 LUAD patients treated with anti-PD-1 therapy was validated by multiplex immunohistochemistry (mIHC).

resultsA PCD signature containing 7 genes was constructed using 101 machine learning algorithm combinations and validated across multiple datasets. High PCD scores in patients are associated with poorer prognosis, lower immune cell infiltration, and reduced responsiveness to immunotherapy. In addition, the PCD signature were comprehensively analyzed by scRNA-seq, and the results showed that the high PCD signature was concentrated mainly in advanced LUAD. Moreover, pathways associated with tumor progression and immune resistance were more strongly promoted in the high PCD signature group. The expression of the key gene NAPSA correlated with immune cell infiltration and immunotherapy response, as confirmed by IHC and mIHC.

conclusionThe PCD signature confers significant potential to predict prognosis of LUAD in patients, and NAPSA is promising as a new marker for predicting the efficacy of immunotherapy.

Indexed as

Adenocarcinoma of LungApoptosisImmunotherapyLung NeoplasmsMachine LearningBiomarkers, TumorGene Expression Regulation, NeoplasticHumansMultiomicsPrognosisBiomarkers, TumorImmunotherapyLung adenocarcinomaMachine learningMultiomicsProgrammed cell death

Identifiers

PMID41501264
PMCPMC12823722

What Socratic holds

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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 Socratic graph.