ArticleThe Journal of pathology2022
Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer: an international multicenter study.
Article in The Journal of pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Prognostic values and clinical significance of POU2F3 expression in neuroendocrine carcinomas: a meta-analysis with a focus on small cell lung cancer.Annals of medicine · 2025Pooled it
- Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study.Molecular cancer · 2024Trial
- Quantitative Immunohistochemical Landscapes and Chemoimmunotherapy Outcomes of ASCL1, NEUROD1, POU2F3, and YAP1 in Pure Small-Cell Lung Cancer: A Pilot Study.Journal of clinical medicine · 2026Article
- [Expert Consensus on Immunotherapy for Extensive-stage Small Cell Lung Cancer Based on Molecular Subtyping].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- [Advances in Systemic Therapy for Extensive-stage Small Cell Lung Cancer in the Era of Precision Treatment].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Immunohistochemical profiling of small cell lung cancer reveals subtype heterogeneity and a tuft cell-like subtype characterized by LRMP and TRPM5.Virchows Archiv : an international journal of pathology · 2026Article
- Extensive-stage small cell esophageal carcinoma: a retrospective analysis of treatment modalities.BMC cancer · 2026Article
- GCNPath: introspecting drug response prediction with pathway-guided graph convolution networks.Communications biology · 2026Article
- Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments.Cancer research · 2026Review
- Subclassification of Small Cell Lung Cancer Based on Gene Expression Signatures and Machine Learning.Cancer research communications · 2026Article
- Eukaryote initiation factor 6 modulates small-cell lung carcinoma plasticity via the integrin-FAK signaling axis.Nature communications · 2026Article
- [New Landscape in the Treatment of Limited-stage Small Cell Lung Cancer: From Conventional Chemoradiotherapy to Latest Advances in Precision Medicine].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Clinical, genetic and immunohistochemical characterization of sinonasal tumors with neuroectodermal differentiation.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Fibroblast growth factor signals drive the metastatic behavior in small cell lung cancer.British journal of cancer · 2026Article
- Case Report: Neuroendocrine-low POU2F3-positive small cell lung cancer presenting as a diagnostically unstable thoracic malignancy.Frontiers in oncology · 2026Article
- CMA-associated cellular state remodeling defines prognostic heterogeneity and identifies ARRDC3 as a protective functional gene in small cell lung cancer.Frontiers in cell and developmental biology · 2026Article
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Quantitative analysis for identifying molecular subtypes of small cell lung cancer via two-dimensional and three-dimensional contrast-enhanced computed tomography images: a preliminary study.Journal of thoracic disease · 2025Article
- Prognostic utility of baseline ASCL1/INSM1 expression and neutrophil-lymphocyte ratio in unresectable SCLC treated with first-line chemoimmunotherapy with or without radiotherapy.Frontiers of medicine · 2025Article
- Prophylactic cranial irradiation together with molecular subtyping in surgically resected small-cell lung cancer: a inverse-probability-of-treatment weighted cohort study.Respiratory research · 2025Article
2 more citing papers are in PubMed but not listed here.
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34 authors at 12 institutions in 7 countries.
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Abstract
The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small-cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant), and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1, and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines revealed distinct vulnerability profiles defined by transcription regulators. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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