Abstract
Genes copy number variation in tumor cells of patients with metastatic and non-metastatic lung adenocarcinoma.
Author
person
Denis S. Kutilin
Rostov Research Institute of Oncology, Rostov-on-Don, Russian Federation
info_outline
Denis S. Kutilin, Igor A. Leyman, Yuriy N. Lazutin, Anna V. Chubaryan, Pavel A. Anistratov, Oleg N. Stateshny, Igor N. Turkin, M. A. Gappoeva, Oleg Ivanovich Kit
Full text
Authors
person
Denis S. Kutilin
Rostov Research Institute of Oncology, Rostov-on-Don, Russian Federation
info_outline
Denis S. Kutilin, Igor A. Leyman, Yuriy N. Lazutin, Anna V. Chubaryan, Pavel A. Anistratov, Oleg N. Stateshny, Igor N. Turkin, M. A. Gappoeva, Oleg Ivanovich Kit
Organizations
Rostov Research Institute of Oncology, Rostov-on-Don, Russian Federation
Abstract Disclosures
Research Funding
Other
Background:
Currently known markers of lung adenocarcinoma are insufficient to predict the development of this disease, which makes the search for new molecular markers a relevant problem. Our purpose was to analyze changes in genes copy number variation (CNV) in tumor and non-tumor cells of the lung in patients with (T1-3N1-2M0-1) and without (T1-3N0M0) metastasis to identify potential molecular markers for the prediction of the disease development.
Methods:
The study was performed on tissue sections from FFPE blocks of 90 patients diagnosed with lung adenocarcinoma. Tumor and non- tumor cells were isolated using laser microdissection (Palm MicroBeam, Carl Zeiss). Copy numbers of 32 genes (BAX, BCL2, C-FLAR, P53, MDM2, BFAR, SEMA3B, RASSF1A, CASP9, CASP3, CASP8, SOX2, OCT4, NANOG, PIK3, MKI67, HV2, HIF1A1, XRCC1, MMP1, TERT, CTNNB1, VEGFA, KRAS, EGFR, GRB2, SOS1, MAPK1, STAT1, BRAF, FTO, mir3678) were determined by Real-Time qPCR (ACTB, B2M, GAPDH - reference genes). Statistical analysis was performed using the Mann-Whitney test.
Results:
A pooled sample (n = 90) showed significant (p < 0.005) increase in the copy numbers of
MAPK1
and
SOX2
and decreased copy numbers of the
mir3678, HV2, BAX
and
CASP3
genes in tumor cells compared to non-tumor. Patients with metastatic and non-metastatic lung adenocarcinoma had significant (p < 0.05) differences in genes copy number in tumor cells compared to non-tumor ones: patients with T1-3N1-2M0-1 (n = 50) – decreased copy numbers of the
mir3678, HV2, MDM2, P53, XRCC1, CASP3
and
OCT4
genes and increased
SOX2
copy number; patients with T1-3N0M0 (n = 40) – increased copy numbers of the
MAPK1
and
mir3678
genes and decreased
HV2
copy number.
Conclusions:
The detected changes in copy numbers of genes responsible for the regulation of apoptosis, proliferation, oxidative phosphorylation and the function of the EGFR signaling pathway in lung tumor cells revealed new molecular markers to predict the risk of metastasis (
mir3678, MDM2,
Р53, SOX2, XRCC1, CASP3, OCT4, MAPK1
).