Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
sequence of miR-330-3p, and decreased by knockdown of miR-330-3p. In nude
mice receiving subcutaneous A549 and HCC827 cell inoculation, tumor growth
were significantly faster in mice receiving A549 and HCC827 cell permanently
expressing exogenous miR-330-3p, and slower in cells permanently
expressing an anti- miR-330-3p sequence. The mice receiving cancer cells
stably expressing exogenous miR-330-3p injection directly into the brain
almostly developed multiple metastatic foci, while developed a smaller
orthotopic tumor in mice receiving injection of cells expressing an anti- miR-
330-3p sequence. GRIA3 was identified as a direct target of miR-330-3p using
luciferase reporter assays. Real-time PCR and Western blot confirmed that
miR-330-3p downregulated GRIA3 expression. MEK inhibition suggested that
GRIA3 was regulated by miR-330-3p via MAPK/MEK/ERK signaling pathway.
Conclusion: These results support the oncogenic role of miR-330-3p in NSCLC
brain metastasis, providing a rationale for miRNA-targeted therapeutic
strategies.
Keywords: MAPK/MEK/ERK signaling pathway, Brain metastasis, microRNA-
330-3p, non-small cell lung cancer
POSTER SESSION 2 – P2.03B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
BIOMARKERS –
TUESDAY, DECEMBER 6, 2016
P2.03B-025 MUTATION PROFILE AND HISTOLOGY SUBTYPE
ACCORDING TO IASLC/ERS/ATC AS RISK FACTORS FOR BRAIN
METASTASES IN LUNG ADENOCARCINOMA
Laura-Alejandra Ramirez-Tirado 1 , Jorge-Negueb Martínez-Hernández 1 , Enrique
Caballe-Perez 1 , Andrés Cardona 2 , Oscar Arrieta 3
1 Thoracic Oncology Unit and Laboratory of M¡personalized Medicine, Instituto
Nacional de Cancerología, Mexico City/Mexico, 2 Clinical and Translational Oncology
Group, Clinica Del Country, Bogotá/Colombia, 3 Thoracic Oncology Unit and
Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico
City/Mexico
Background: Brain metastases (BM) are common among patients with
adenocarcinoma, affecting treatment response, quality of life and overall
survival(OS). We examine the impact of the main histological pattern and the
genetic alterations in EGFR and ALK on the incidence of BM in patients with
advanced non-small cell lung cancer (NSCLC). Methods: From January 2004
through December 2014 the medical records of 991 patients with NSCLC were
reviewed for eligibility, among them 711 had adenocarcinoma histology. We
describe the factors associated with the overall incidence of BM as well as the
incidence of BM stratified on the histological grade pattern according to the
ERS/ATC/IASLC classification (lepidic vs acinar+papilar vs micropapilar+solid).
Results: Among 711 patients, 53.6% were female, 47.1% were less than 60
years-old at the time of diagnosis, exposure to tobacco, wood-smoke and
asbestos were found in 52.0%, 40.5% and 13.8%, respectively. Seventy-six
percent had a good performance status, and nearly sixty percent (59.8%) had
oligometastatic disease. Most of the patients had a stage IV disease at the
time of diagnosis (79.3%). Regarding histological grade classification, male
patients were more likely to have a poorly differentiated adenocarcinoma in
comparison with women (61.2% vs. 51.2%, p=0.027), as well as ever-smokers
compared with non-smokers (61.4% vs. 49.9%). Likewise, patients harboring
an ALK rearrangement were more likely to have a highly- or moderate
differentiated adenocarcinoma (100% vs. 43.6%, p=0.008). A total of 122
patients (17.1 %) had a brain metastasis at diagnosis and 37.4% had baseline
carcinoembryonic levels above 20 pg/ml.By Kaplan-Meier method 6.45% and
12.10% of patients developed BM at 12 and 24 months. The factors associated
with a high incidence of BM were: female gender (40.9% vs. 34.4%; p=0.036),
age < 60 years (44.4% vs. 32.1%, p=