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T.G. Prieto
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 2
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-027 - 13-Gene Signature of EMT Reveals Impact on Invasion and Metastasis of Neuroendocrine Carcinomas of the Lung: A Preliminary Study (ID 5466)
14:30 - 14:30 | Author(s): T.G. Prieto
- 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 emerge 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 for EMT (Qiagen, Dusseldorf, Germany). Associations of the gene signature and clinicopathological features, as well as prognostic factors were evaluated.
Results:
A 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, PDGFRB, SNAI1, SNAI3, TCF3, TGFβ1, TGFβ2, TGFβ3 and VIM) that was related to EMT was up-regulated in tumor-tissue from all NELC patients, mainly in those with high-grade NELC. An increased expression of DSP, TCF3 and TGFβ3 was found in SCLC compared to AC, TC and LCNEC, and associated with lymph nodes metastasis with statistical significance respectively for DSP (p=0.03 and 0.02), TCF3 (p=0.02) and marginal significance for TCF3 and TGFβ3 (p=0.08 and p=0.08). TCF3 was also associated with tobacco history (p=0.04). A significant correlation was found between enolase and IL1RN (p=0.03), chromogranin and TGFβ2 (p=0.04), synaptophysin and TGFβ1 and TGFβ2 respectively (p=0.04 and p=0.02).
Conclusion:
The EMT analysis identified genes involved in cell proliferation, motility, invasion and metastasis of NELC. We further inferred DSP, TCF3 and TGFβ3 as target against lung cancer metastasis and invasion, thus arising as promising therapeutic agent.
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P1.07-030 - Gene Signature of EMT in Neuroendocrine Lung Carcinoma: A Comparative Analysis with Adenocarcinoma and Squamous Cell Carcinoma (ID 5366)
14:30 - 14:30 | Author(s): T.G. Prieto
- Abstract
Background:
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.
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 for EMT (Qiagen, Dusseldorf, Germany).
Results:
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).
Conclusion:
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.
