PT  - JOURNAL ARTICLE
AU  - C Lang
AU  - Z Megyesfalvi
AU  - B Szeitz
AU  - A Lantos
AU  - N Woldmar
AU  - Z Valko
AU  - A Schwendenwein
AU  - F Oberndorfer
AU  - N Barany
AU  - S Paku
AU  - V Laszlo
AU  - H Kiss
AU  - E Bugyik
AU  - B Ferencz
AU  - K Dezso
AU  - Z Lohinai
AU  - J Moldvay
AU  - J Fillinger
AU  - G Galffy
AU  - C Rivard
AU  - F R Hirsch
AU  - L Brcic
AU  - H Popper
AU  - I Kern
AU  - M Kovacevic
AU  - J Skarda
AU  - M Mittak
AU  - A M Szasz
AU  - L Pizzatti
AU  - K Bogos
AU  - M A Hoda
AU  - K Hoetzenecker
AU  - G Marko-Varga
AU  - P Horvatovics
AU  - F Renyi-Vamos
AU  - T Klikovits
AU  - K Schelch
AU  - M Rezeli
AU  - B Döme
TI  - Subtype-specific transcription factors are clinically relevant and show distinct therapeutic vulnerabilities in human small cell lung cancer
AID  - 10.1183/13993003.congress-2022.3828
DP  - 2022 Sep 04
TA  - European Respiratory Journal
PG  - 3828
VI  - 60
IP  - suppl 66
4099  - http://erj.ersjournals.com/content/60/suppl_66/3828.short
4100  - http://erj.ersjournals.com/content/60/suppl_66/3828.full
SO  - Eur Respir J2022 Sep 04; 60
AB  - Background: Key transcription factors ASCL1, NEUROD1, POU2F3, YAP1 have been recently reported to characterize uniquely different small cell lung cancer (SCLC) subtypes (SCLC-A; SCLC-N; SCLC-P; SCLC-Y). However, their clinical presence and therapeutic relevance has not yet been widely investigated.Methods: Immunohistochemistry (IHC) was performed on surgically resected specimens of n=386 SCLC patients. Furthermore, large-scale proteomic and in-depth bioinformatical analyses were conducted in n=26 human SCLC cell lines. Standard-of care and targeted agents were used to evaluate distinct therapeutic vulnerabilities in vitro.Results: IHC revealed SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant), SCLC-P (POU2F3-dominant) and quadruple-negative SCLC specific subtypes (SCLC-QN) to be present in surgically resected SCLC specimens. Interestingly, SCLC-A subtype significantly correlated with poor and SCLC-P subtype with favorable clinical outcome. Proteomic pathway enrichment analysis identified unique expressional signatures for each SCLC subtype. Cell viability assays demonstrated remarkable sensitivity and resistance differences to standard-of-care chemotherapeutics and targeted agents between distinct SCLC subtypes.Conclusions: Differential expression signatures of four key-transcription factors ASCL1, NEUROD1, POU2F3 and YAP1 are present and clinically relevant in SCLC. Our findings may contribute to a better insight into the biology and therapeutic diversity of SCLC.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 3828.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).