Abstract A83: Genes of epithelial-mesenchymal transition (EMT) reveal impact on progression and metastasis of neuroendocrine lung carcinomas: A preliminary study

Abstract

Abstract Background: Metastasis are responsible for the death of 90% of patients with lung cancer, indicating the need to know the multiple signaling pathways involved. Neuroendocrine lung carcinomas (NELC) encompass a wide spectrum of tumors, from the low-grade typical carcinoid (TC) and atypical carcinoid (AC), to the high-grade large cell neuroendocrine carcinoma (LCNEC) and the small-cell lung carcinoma (SCLC). Low-grade NELC are indolent, while high-grade NELC invade and metastasize rapidly. Biomarkers of NELC aggressiveness remain to be determined. Epithelial to mesenchymal transition (EMT) genes profile show promise as indicator of invasion and metastasis. Our aim was to evaluate: (1) EMT gene expression in NELC, (2) its relationship with the histologic subtypes, and (3) its impact on behavior of the tumors. Methods: Patients with SCLC (n = 10), LCNEC (n=5), AC (n=2) and TC (n=7) were included. EMT gene expression was quantified with a quantitative real-time (RT)-PCR carried out on StepOnePlus™ Real-Time PCR System (Applied Biosystems) with RT2 Profiler PCR Array System (Qiagen, Dusseldorf, Germany). Associations of the gene signature and clinicopathologic features, as well as prognostic factors were evaluated. Results: A 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, PDGFRB, SNAI1, SNAI3, TCF3, TGF-beta 1, TGF-beta 2, TGF-beta 3, and VIM) that was related to EMT was upregulated in tumor-tissue from all NELC patients, mainly in those with high-grade NELC. An increased expression of DSP, TCF3, and TGF-beta 2 genes were shown in high-grade when compared to low-grade NELC and associated with lymph node metastasis with statistical significance respectively for DSP (p<0.05), TGF-beta 3 (p<0.05), and marginal significance for TCF3 (p=0.08). TCF3 was also associated with tobacco history (p=0.04). Conclusion: The EMT analysis identified genes involved in cell proliferation, motility, invasion, and metastasis of NELC. We further inferred DSP, TCF3, and TGF-beta 3 as target against lung cancer metastasis and invasion, thus arising as a promising therapeutic agent. Citation Format: Tabatha Gutierrez Prieto, Vanessa Karen de Sá, Eloisa Helena Ribeiro Olivieri, Eduardo Caetano Albino da Silva, Rui Manuel Reis, Dirce Maria Carraro, Vera Luiza Capelozzi. Genes of epithelial-mesenchymal transition (EMT) reveal impact on progression and metastasis of neuroendocrine lung carcinomas: A preliminary study [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A83.