Abstract 4922: NEUROD1 is highly expressed in extensive small cell lung cancer by promoting migration

Abstract

Abstract Introduction:Small cell lung cancer (SCLC) exhibits high-grade neuroendocrine features and recent genomic analyses revealed that aberrant expression of bacic helix loop helix transcription factors such as neurogenic differentiation 1 (NEUROD1) as well as achaete-scute homolog 1(ASCL1) have also been observed in SCLC. NEUROD1 plays important role for the development, maturation in several nerve system and formation of distal lung of neuroendocrine morphology. Previous report showed that mRNA expression as well as target genes of NEUROD1 are largely distinct from those of ASCL1 in human SCLC cell lines, however, protein level and expression patterns of these transcription factors in SCLC clinical tumor samples as well as its relation to clinicopathological characteristics have not been fully elucidated. Method: We retrospectively analyzed specimens from 95 SCLC patients between June 1988 and December 2017, and immunohistochemical (IHC) staining of NEUROD1 as well as ASCL1 was performed. Furthermore, we examined the effect of gain or loss of NEUROD1 function on proliferation and migration by transfection in SCLC cell lines. Result:Dual high staining score of ASCL1 and NEUROD1 was present in SCLC samples (32/95: 34%) and IHC score of NEUROD1 was higher in extensive disease (ED) samples than those in limited disease (LD) samples (median score 160 vs 80 ; P = 0.0389).Overall survival did not significantly differ between SCLC patients with high or low score of NEUROD1 or ASCL1. Next, our vitro data showed that upregulation of NEUROD1 in SCLC cell lines promoted transwell migration whereas downregulation of NEUROD1 reduced cell migration. Conclusion: Our results from clinical and in vitro experimental data collectively indicate that NEUROD1 expression increases in extensive SCLC by promoting migration and metastasis of SCLC cells. Citation Format: Yuki Ikematsu, Kentaro Tanaka, Nobuhisa Ando, Kayo Ijichi, Yasuto Yoneshima, Hiroyuki Inoue, Goji Toyokawa, Tetsuzo Tagawa, Yoichi Nakanishi, Isamu Okamoto. NEUROD1 is highly expressed in extensive small cell lung cancer by promoting migration [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4922.