Evidence map›Paper›PMID 42375369›Full record

ArticleFrontiers in immunology2026

Integrated genomic and immunophenotypic profiling reveals monoclonal origin, smoking-driven evolution and heterogeneous microenvironment in pulmonary adenosquamous carcinoma.

Xiuwen Zhang, Heng Wu, Wenhao Zhao, Zixuan Hu, Guannan Wang, Yongwen Li, Xuanguang Li, Hongbing Zhang, Minghui Liu, Chen Chen and 4 more

Abstract read
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Article in Frontiers in immunology, 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

14 authors.

Xiuwen Zhang *Department of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Heng Wu *Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Wenhao Zhao *Department of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Zixuan Hu *Department of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Guannan WangDepartment of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Yongwen LiTianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Xuanguang LiDepartment of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Hongbing ZhangDepartment of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Minghui LiuDepartment of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Chen ChenTianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Jinghao LiuDepartment of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Wenhao ZhouKindstar Global Precision Medicine Institute, Wuhan, Hubei, China.
Hongyu LiuTianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Jun ChenDepartment of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Pulmonary adenosquamous carcinoma (ASC) is a rare, aggressive subtype of non-small cell lung cancer (NSCLC), characterized by both adenocarcinoma (ACC) and squamous cell carcinoma (SCCC) components. Due to its rarity, the clonal origin, evolutionary drivers, and tumor microenvironment (TME) of ASC remain poorly understood. Methods: We conducted clinical and prognostic analyses on 76 ASC patients. Nine patients with available tissues underwent microdissection to isolate matched ACC and SCCC regions, which were then analyzed using whole-exome sequencing (WES), copy-number analysis, phylogenetic reconstruction, and multiplex immunofluorescence (mIF) for immune profiling. Results: Multivariate Cox regression identified the histological subtype of the ACC component as an independent prognostic factor, with solid and micropapillary subtypes associated with the poorest overall survival. WES revealed frequent mutations in TP53 (56%), EGFR (33%), MET (33%), and PIK3CA (22%) across tumor regions. Shared truncal mutations and copy-number alterations between ACC and SCCC regions suggest a common monoclonal origin. Smokers had a significantly higher tumor mutational and neoantigen load than non-smokers, with greater overlap in mutations between ACC and SCCC. Phylogenetic analysis showed distinct evolutionary patterns: smokers' tumors displayed smoking-related and APOBEC mutational signatures, while non-smokers had aging-related signatures. mIF analysis revealed significantly higher immune cell infiltration (CD8 Conclusion: Our findings support a monoclonal origin for ASC, with smoking influencing divergent evolutionary trajectories and immune microenvironment characteristics between ACC and SCCC. These insights provide a molecular framework for personalized ASC therapies.

Indexed as

Carcinoma, AdenosquamousLung NeoplasmsSmokingTumor MicroenvironmentAgedBiomarkers, TumorExome SequencingFemaleGenomicsHumansImmunophenotypingMaleMiddle AgedMutationPhylogenyPrognosisBiomarkers, Tumorevolutionary trajectorymultiplex immunofluorescencepulmonary adenosquamous carcinomatumor microenvironmentwhole-exome sequencing

Identifiers

PMID42375369
PMCPMC13311056

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