20.500.12556/DiRROS-15120 Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small cell lung cancer : an international multicenter study 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. Non-small-cell lung carcinoma immunohistochemistry molecular subtypes prognostic relevance expression pattern neuroendocrine subtypes nedrobnocelični karcinom pljuč imunohistokemija molekularni podtipi napovedni pomen vzorec izražanja nevroendokrini podtipi true false true John Wiley &Sons Angleški jezik Ni določen © 2022 The Authors. Neznano 2022-05-27 12:59:24 2022-05-27 12:59:26 2022-08-21 03:35:25 0000-00-00 00:00:00 2022 0 ZDA 0 Nasl. z nasl. zaslona; Soavtorja iz Slovenije: Izidor Kern, Mile Kovačević; Opis vira z dne 11. 5. 2022; str. [1-28] iss. Vol. 257 2022 0000-00-00 PostprintKoncna VTisku NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616 1096-9896 10.1002/path.5910 107358467 RAZ_Megyesfalvi_Zsolt_i2022.pdf RAZ_Megyesfalvi_Zsolt_i2022.pdf 1 2FFA7F10276A77677F161BAF5C4D00C1 0affc9c4725c4f5813bbf9d88ad5fa1f3f7e2ac7e7eed18072fce7e13b0712c2 eb261b2c-17b6-11ed-b6b8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=19758 https://onlinelibrary.wiley.com/doi/10.1002/path.5922 1 https://dirros.openscience.si/Dokument.php?lang=slv&id=19757 Univerzitetna klinika za pljučne bolezni in alergijo Golnik 0 0 0