Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
TargetScan (a microRNA database) that would potentially bind to IGBP1.
Using reverse transcription-quantitative PCR (RT-qPCR), we analyzed the
expression levels of candidate microRNAs in frozen specimens of lung
adenocarcinoma. We also validated these microRNAs by checking IGBP1
expression and cell proliferation after they had been transfected into lung
adenocarcinoma cell lines (A549, PC-9) and confirmed the direct effect of the
microRNAs by luciferase reporter assay. Results: Using microRNA array and
TargetScan, we selected 6 microRNAs (miR-34b, miR-138, miR-374a, miR-374b,
miR-1909, miR-3941). RT-qPCR analysis showed that these microRNAs were
down-regulated in invasive adenocarcinoma (IGPB1+) relative to adjacent
normal lung tissue (IGBP1-) (Fig1A). We transfected these microRNAs into lung
adenocarcinoma cell lines, and all of the microRNAs suppressed IGBP1
expression. Among these microRNAs, miR-34b and miR-3941 depressed
luciferase activity by targeting 3’UTR-IGBP1 in the luciferase vector (Fig1B).
contrasts the aberrations of their copy numbers. 70 genes were validated
using TCGA-LUAD data. We showed that paradoxical expression of these
genes is associated with 19 microRNAs, whose significant deregulation in
LUAD has been consistently reported. Importantly, these genes form a
clinically significant prognostic signature.
Conclusion: We have found that miR-3941 targets IGBP1 in addition to
miR-34b. Down-regulation of both microRNAs can lead to high expression of
IGBP1, and this is thought to be associated with progression of lung
adenocarcinoma.
Keywords: IGBP1, microRNA, Adenocarcinoma, lung
Conclusion: Paradoxical gene expression, caused by microRNA deregulation, is
preserved across patient cohorts, and forms a prognostic LUAD signature.
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
ANALYSIS OF RNA –
TUESDAY, DECEMBER 6, 2016
Keywords: microRNA, prognostic signature, Copy number aberrations, lung
adenocarcinoma
P2.01-015 DIFFERENTIALLY EXPRESSED MICRORNAS IN LUNG
ADENOCARCINOMA INVERT EFFECTS OF COPY NUMBER
ABERRATIONS OF PROGNOSTIC GENES
Tomas Tokar 1 , Emily Vucic 2 , Chiara Chiara Pastrello 1 , Varune Ramnarine 1 ,
Chang-Qi Zhu 3 , Kenneth Craddock 3 , Frances Shepherd 4 , Ming Tsao 3 , Wan
Lam 2 , Igor Jurisica 1
1 Jurisica Lab, University Health Network, Toronto/ON/Canada, 2 Department
of Integrative Oncology, British Columbia Cancer Research Center, Vancouver/
BC/Canada, 3 Tsao Laboratory, University Health Network, Toronto/ON/Canada,
4 Cancer Clinical Research Unit, University Health Network, Toronto/ON/Canada
Background: Across multiple cancer histologies, many significantly downregulated
genes reside within chromosomal regions with increased number of
copies, and vice versa. These “paradoxical genes” have been usually ignored as
a noise, but could be a consequence of epigenetic regulatory mechanisms,
including microRNA-mediated control of mRNA transcription. Methods: To
identify paradoxical genes in lung adenocarcinoma (LUAD) we curated and
analyzed gene expression and copy number aberrations across 1,064 LUAD
samples, including newly-generated aCGH data from 65 samples. We then
analyzed 9 LUAD microRNA expression studies to compile a list of consistently
deregulated microRNAs. Finally, using microRNA:gene networks from mirDIP
we examined possible association between microRNAs and paradoxical genes.
Results: We identified 85 genes whose differential expression consistently
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
ANALYSIS OF RNA –
TUESDAY, DECEMBER 6, 2016
P2.01-016 ANALYSIS OF 5 DIFFERENTIAL MIRNA EXPRESSION IN
NSCLC PATIENTS
Marzena A Lewandowska 1 , Lukasz Zolna 2 , Aleksandra Chrząstek 2 , Janusz
Kowalewski 2
1 Molecular Oncology and Genetics Departament, The F. Lukaszczyk Oncology
Center, Collegium Medicum, Nicolaus Copernicus Univeristy, Bydgoszcz/Poland,
2 Department of Thoracic Surgery and Tumors, Collegium Medicum in Bydgoszcz,
Nicolaus Copernicus University in Torun, Bydgoszcz/Poland
Background: There are two main types of lung cancer: non small cell lung
cancer (NSCLC) which represents 80-85% cases of lung cancer and small cell
lung cancer (SCLC) which is about 10-15% cases of lung cancer. The 5-year
survival rate for patients with lung cancer vary depending on the stage of the
cancer when it is diagnosed. Unfortunately, most of patients with lung cancer
are diagnosed on later stage of disease (stage III and IV). In our research we try
to find marker among miRNA that can predict occurring of lung cancer on the
earlier stage. Methods: Isolation of miRNA from plasma was performed by
miRCURY RNA Isolation Kit – Biofluids (Exiqon) from NSCLC patients and
Copyright © 2016 by the International Association for the Study of Lung Cancer
S413