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  • Megyesfalvi, ZsoltNational Institute of Oncology, Budapest,Medical University of Vienna,National Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)

Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer : an international multicenter study

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-05-25
  • Wiley,2022
  • 13 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:faf38cfe-d716-4c27-a886-02947864930a
  • https://lup.lub.lu.se/record/faf38cfe-d716-4c27-a886-02947864930aURI
  • https://doi.org/10.1002/path.5922DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Barany, NandorNational Korányi Institute for Tuberculosis and Pulmonology, Hungary,Semmelweis University,Medical University of Vienna (author)
  • Lantos, AndrasNational Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)
  • Valko, ZsuzsannaNational Korányi Institute for Tuberculosis and Pulmonology, Hungary,Medical University of Vienna (author)
  • Pipek, OrsolyaEötvös Loránd University (author)
  • Lang, ChristianMedical University of Vienna (author)
  • Schwendenwein, AnnaMedical University of Vienna (author)
  • Oberndorfer, FelicitasMedical University of Vienna (author)
  • Paku, SandorSemmelweis University (author)
  • Ferencz, BenceNational Korányi Institute for Tuberculosis and Pulmonology, Hungary,National Institute of Oncology, Budapest (author)
  • Dezso, KatalinSemmelweis University (author)
  • Fillinger, JanosNational Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)
  • Lohinai, ZoltanNational Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)
  • Moldvay, JuditNational Korányi Institute for Tuberculosis and Pulmonology, Hungary,Hungarian Academy of Sciences (author)
  • Galffy, Gabriella (author)
  • Szeitz, BeataSemmelweis University (author)
  • Rezeli, MelindaLund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Masspektrometri,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,BioMS,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Mass Spectrometry,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund(Swepub:lu)elma-mrl (author)
  • Rivard, ChristopherUniversity of Colorado (author)
  • Hirsch, Fred R.University of Colorado (author)
  • Brcic, LukaMedical University of Graz (author)
  • Popper, HelmutMedical University of Graz (author)
  • Kern, IzidorUniversity Clinic Golnik (author)
  • Kovacevic, MileUniversity Clinic Golnik (author)
  • Skarda, JozefUniversity Hospital Ostrava,Palacký University (author)
  • Mittak, MarcelUniversity Hospital Ostrava (author)
  • Marko-Varga, GyorgyLund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Lund University Research Groups(Swepub:lu)akem-gmv (author)
  • Bogos, KrisztinaNational Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)
  • Renyi-Vamos, FerencNational Institute of Oncology, Budapest,National Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)
  • Hoda, Mir AlirezaMedical University of Vienna (author)
  • Klikovits, ThomasMedical University of Vienna (author)
  • Hoetzenecker, KonradMedical University of Vienna (author)
  • Schelch, KarinMedical University of Vienna (author)
  • Laszlo, ViktoriaNational Korányi Institute for Tuberculosis and Pulmonology, Hungary,National Institute of Oncology, Budapest,Medical University of Vienna (author)
  • Dome, BalazsNational Korányi Institute for Tuberculosis and Pulmonology, Hungary,National Institute of Oncology, Budapest,Medical University of Vienna(Swepub:lu)ba1464do (author)
  • National Institute of Oncology, BudapestMedical University of Vienna (creator_code:org_t)

Related titles

  • In:Journal of Pathology: Wiley257:5, s. 674-6860022-34171096-9896

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