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Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small cell lung cancer [Elektronski vir] : an international multicenter studyMegyesfalvi, Zsolt ...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 have 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 reveal distinct vulnerability profiles defined by transcription regulators.Source: The Journal of pathology [Elektronski vir]. - ISSN 1096-9896 (Vol. 257, iss. 5, Aug. 2022, str. 674-686)Type of material - e-article ; adult, seriousPublish date - 2022Language - englishCOBISS.SI-ID - 107358467
Author
Megyesfalvi, Zsolt |
Barany, Nandor |
Lantos, Andras |
Valko, Zsuzsanna |
Pipek, Orsolya |
Lang, Christian, (medicina) |
Schwendenwein, Anna |
Oberndorfer, Felicitas |
Paku, Sandor |
Ferencz, Bence |
Kern, Izidor |
Kovačević, Mile |
Laszlo, Viktoria |
Dome, Balazs
Topics
Carcinoma, non-small-cell lung |
Immunohistochemistry |
Nedrobnocelični karcinom pljuč |
Imunohistokemija |
molekularni podtipi |
napovedni pomen |
vzorec izražanja |
nevroendokrini podtipi |
molecular subtypes |
prognostic relevance |
expression pattern |
neuroendocrine subtypes
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Megyesfalvi, Zsolt | |
Barany, Nandor | |
Lantos, Andras | |
Valko, Zsuzsanna | |
Pipek, Orsolya | |
Lang, Christian, (medicina) | |
Schwendenwein, Anna | |
Oberndorfer, Felicitas | |
Paku, Sandor | |
Ferencz, Bence | |
Kern, Izidor | 15781 |
Kovačević, Mile | |
Laszlo, Viktoria | |
Dome, Balazs |
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