Abstract A82: Epithelial-mesenchymal transition (EMT) genes are involved in the behavior and aggressiveness of neuroendocrine lung carcinomas (NELC) and non-small cell lung cancer (NSCLC): A comparative analysis
Authors: Prieto Tabatha Gutierrez , Sá Vanessa Karen de , Olivieri Eloisa Helena Ribeiro , Silva Eduardo Caetano Albino da , Reis Rui Manuel , Carraro Dirce Maria , Capelozzi Vera Luiza 
Published: May 2019

Background: Recurrence and metastasis are responsible for 90% of deaths of patients with lung cancer. Adenocarcinomas (ADc) primarily invade blood vessels with distant metastasis, whereas squamous cell carcinoma (SqCC) involves the mediastinal lymph nodes. Neuroendocrine carcinomas of low grade (typical and atypical carcinoid) are indolent, while high-grade NE carcinoma (large-cell NE and small-cell carcinomas) metastasize rapidly. Biomarkers of invasiveness in lung carcinomas still cannot be definitely determined. Epithelial to mesenchymal transition (EMT) genes profile have promise as indicator of invasion and metastasis. Our aim was to compare EMT gene expression in NELC, ADc, and SqCC and its impact on behavior of these tumors.

Methods: 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).

Results: Younger patients expressed higher amount of AHNAK, MSN, and TGF-beta 3 than older (p&lt;0.05), whereas SNAI3 and TGF-beta 2 were more expressed in smokers (p&lt;0.05). ADc and SqCC presented significant higher expression of COL3A1, DSP, and MSN in tumor compared to normal tissue (p&lt;0.05). 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, PDGFRB, SNAI1, SNAI3, TCF3, TGF-beta 1, TGF-beta 2, TGF-beta 3, and VIM) was upregulated in tumor tissue from all NELC patients. In ADc and NELC, AHNAK, IL1RN, SNAI3, and VIM was significantly different (p&lt;0.05). ADc and SqCC compared with high-grade NELC also presented differences in COL3A1, DSP, and PDGFR (p&lt;0.01). Advanced tumors, usually with metastasis, showed higher expression of AHNAK, MSN, SNAI3, TGF-beta 3, and VIM (p&lt;0.05), as well as association with poor outcome (p &lt;0.01).

Conclusion: Different expression of EMT gene signature in neuroendocrine lung carcinomas and non-small cell lung cancer, its relationship with histologic types, advanced stage, lymph node metastasis, and death suggest a possible role of these markers in this malignancy, but more importantly provide a potential biomolecular marker to predict outcome. The correlation between NELC, ADc, SqCC, and specific EMT genes involved in cell proliferation and motility provides a possible role of these genes in the development and aggressiveness in these tumors. Moreover, the difference of gene expression between NSCLC and NELC emerges as a promising biomarker of behavior. Further studies are needed to validate EMT gene expression to predict prognosis and tumoral aggressiveness.

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. Epithelial-mesenchymal transition (EMT) genes are involved in the behavior and aggressiveness of neuroendocrine lung carcinomas (NELC) and non-small cell lung cancer (NSCLC): A comparative analysis [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 A82.