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

Megyesfalvi, Zsolt (författare)
Medical University of Vienna,National Institute of Oncology, Budapest,National Korányi Institute for Tuberculosis and Pulmonology, Hungary
Barany, Nandor (författare)
Semmelweis University,Medical University of Vienna,National Korányi Institute for Tuberculosis and Pulmonology, Hungary
Lantos, Andras (författare)
National Korányi Institute for Tuberculosis and Pulmonology, Hungary
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Valko, Zsuzsanna (författare)
National Korányi Institute for Tuberculosis and Pulmonology, Hungary,Medical University of Vienna
Pipek, Orsolya (författare)
Eötvös Loránd University
Lang, Christian (författare)
Medical University of Vienna
Schwendenwein, Anna (författare)
Medical University of Vienna
Oberndorfer, Felicitas (författare)
Medical University of Vienna
Paku, Sandor (författare)
Semmelweis University
Ferencz, Bence (författare)
National Institute of Oncology, Budapest,National Korányi Institute for Tuberculosis and Pulmonology, Hungary
Dezso, Katalin (författare)
Semmelweis University
Fillinger, Janos (författare)
National Korányi Institute for Tuberculosis and Pulmonology, Hungary
Lohinai, Zoltan (författare)
National Korányi Institute for Tuberculosis and Pulmonology, Hungary
Moldvay, Judit (författare)
National Korányi Institute for Tuberculosis and Pulmonology, Hungary,Hungarian Academy of Sciences
Galffy, Gabriella (författare)
Szeitz, Beata (författare)
Semmelweis University
Rezeli, Melinda (författare)
Lund 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
Rivard, Christopher (författare)
University of Colorado
Hirsch, Fred R. (författare)
University of Colorado
Brcic, Luka (författare)
Medical University of Graz
Popper, Helmut (författare)
Medical University of Graz
Kern, Izidor (författare)
University Clinic Golnik
Kovacevic, Mile (författare)
University Clinic Golnik
Skarda, Jozef (författare)
Palacký University,University Hospital Ostrava
Mittak, Marcel (författare)
University Hospital Ostrava
Marko-Varga, Gyorgy (författare)
Lund 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
Bogos, Krisztina (författare)
National Korányi Institute for Tuberculosis and Pulmonology, Hungary
Renyi-Vamos, Ferenc (författare)
National Korányi Institute for Tuberculosis and Pulmonology, Hungary,National Institute of Oncology, Budapest
Hoda, Mir Alireza (författare)
Medical University of Vienna
Klikovits, Thomas (författare)
Medical University of Vienna
Hoetzenecker, Konrad (författare)
Medical University of Vienna
Schelch, Karin (författare)
Medical University of Vienna
Laszlo, Viktoria (författare)
Medical University of Vienna,National Institute of Oncology, Budapest,National Korányi Institute for Tuberculosis and Pulmonology, Hungary
Dome, Balazs (författare)
National Korányi Institute for Tuberculosis and Pulmonology, Hungary,National Institute of Oncology, Budapest,Medical University of Vienna
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 (creator_code:org_t)
2022-05-25
2022
Engelska 13 s.
Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 257:5, s. 674-686
Relaterad länk:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

ASCL1
expression pattern
immunohistochemistry
molecular subtypes
NEUROD1
neuroendocrine subtypes
POU2F3
prognostic relevance
small cell lung cancer
YAP1

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