ArticleMolecular cancer2025
Multi-omic profiling provides insights into the heterogeneity, microenvironmental features, and biomarker landscape of small-cell lung cancer.
Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Narrative review of the staging classification controversy in stage N3 small cell lung cancer: from the perspective of overlapping Veterans Administration Lung Study Group and International Association for the Study of Lung Cancer definitions.Journal of thoracic disease · 2026Review
- RNA sequencing reveals differential expression of circular RNAs in human small cell lung cancer.Scientific reports · 2026Article
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Dissecting the role of KLF5: from tumor progression to immune interactions with emphasis on glioma and bladder cancer.Frontiers in immunology · 2025Article
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Authors and funding
18 authors.
Funding
Abstract
backgroundGreater understanding of differential therapeutic sensitivity, specifically to immunotherapy, in small-cell lung cancer (SCLC) is required.
methodsWe explored SCLC heterogeneity through integrated molecular characterization of tumor tissue samples from 159 treatment-naive patients, utilizing genetic, epigenetic, transcriptional, and proteomic profiling, immunohistochemistry staining for multiple biologically relevant markers including transcriptional subtype-defining proteins, and spatial immune profiling using multiplex immunofluorescence.
resultsMulti-omics analysis confirmed high heterogeneity across/within neuroendocrine and non-neuroendocrine subtypes. Methylomics analysis identified four methylome clusters that may enhance subtype prediction, prognosis, and longitudinal monitoring of subtype evolution. Immunohistochemistry analysis showed high MHC-I expression in non-neuroendocrine subtypes, which have greatest potential benefit from adding immunotherapy to chemotherapy; high DLL3 expression associated with neuroendocrine subtypes and an immune-cold tumor microenvironment. Multiplex immunofluorescence demonstrated associations of MHC-I with spatial arrangement and phenotypic features of immune cells in the tumor microenvironment of high-MHC-I-expressing SCLC, providing mechanistic rationale for MHC-I as a potential biomarker of immunotherapy response.
conclusionsThis multimodal profiling analysis provides further insights into the biologic complexity of SCLC and highlights potential therapeutic vulnerabilities of distinct disease subtypes.
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