P1.07-030 Gene Signature of EMT in Neuroendocrine Lung Carcinoma: A Comparative Analysis with Adenocarcinoma and Squamous Cell Carcinoma

Abstract

Recurrence and metastasis are responsible for 90% of the death 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 emerge 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. 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 for EMT (Qiagen, Dusseldorf, Germany). Younger patients expressed higher amount of AHNAK, IL1RN, MSN, TCF3 and VIM than older (p<0.05), whereas SNAI3 and TGFβ2 were more expressed in smokers (p<0.05). ADc and SqCC presented significant higher expression of COL3A1, DSP and MSN in tumor compared to normal tissue (p<0.05). 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, PDGFRB, SNAI1, SNAI3, TCF3, TGFβ1, TGFβ2, TGFβ3 and VIM) was up-regulated in tumor-tissue from all NELC patients. In ADc and NELC, AHNAK, IL1RN, TCF3 and VIM was significantly different (p<0.05). ADc and SqCC compared with high-grade NELC also presented differences in COL3A1 (p<0.01). Interestingly, only NELC expressed PDGFRB, SNAI1, SNAI3, TCF3, TGFβ1, TGFβ2, TGFβ3. Advanced tumors, usually with metastasis, showed higher expression of AHNAK, DSP, IL1RN, MSN and VIM (p<0.05), as well as association with poor outcome (p <0.01). Different expression of EMT gene signature in endocrine and non-endocrine lung carcinomas, 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 on the development and aggressiveness in these tumors. Moreover, the specific genes expressed only in NELC emerges as promise biomarker of behavior. Further studies are needed to validate EMT gene expression to predict prognosis and tumoral aggressiveness.