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Role of LUZP2 Gene in Chronic Obstructive Pulmonary Disease Progressing to Lung Cancer
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A2698 - Role of LUZP2 Gene in Chronic Obstructive Pulmonary Disease Progressing to Lung Cancer
Author Block: L. Zhao1, M. d. Andrade2, J. Na2, J. A. Wampfler2, M. Zhang3, A. H. Limper4, P. Yang3; 1Department of Respiratory disease, Third Affiliated Hospital of Second Military Medical University, Shanghai, China, 2Division of Biomedical Statistics and Informatics, Mayo clinic, Rochester, MN, United States, 3Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN, United States, 4Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States.
Rationale: Chronic obstructive pulmonary disease (COPD) is a known risk factor for lung cancer; the morbidity and mortality of lung cancer in COPD is obviously higher than each disease alone. In order to find the genomic relationship between COPD and lung cancer, we conducted a genomic validation-functional confirmation study to test highly-selected single nucleotide polymorphisms (SNPs) which have been previously screened as candidate in promoting COPD to Lung cancer. Methods: We tested 217 SNPs from our previous study in 2484 individuals from Mayo Clinic and LTRC (Lung Tissue Research Consortium) in four models: lung cancer VS control, COPD VS control, lung cancer with COPD VS control, and lung cancer with COPD VS COPD. We evaluated the relevance to tumor of the gene containing the significant SNPs and their biological functions. Results: A SNP (rs7928736) in LUZP2 gene was validated to be associated with progression from COPD to lung cancer (LUZP2), OR=1.80 and P=1.58×10-3. The basic research data indicate that both transcription level and protein level of LUZP2 were higher in NSCLC tissues and cells than in adjacent non-cancerous tissues and normal lung endothelial cells. The mechanism study shows that knockdown of LUZP2 by a lentiviral approach inhibited the proliferation and invasion in H1650, A549 and NCI-H1299 cells, and caused G1 arrest. In addition, in-vivo tumor bearing experiments show that LUZP2 depletion suppressed the growth of NSCLC tumors. Conclusions: LUZP2 may be a key gene for COPD patients to develop NSCLC, and its high expression in lung cancer tissue or cells, which is associated with SNP rs7928736. Knockdown of LUZP2 suppressed the proliferation and invasion in NSCLC cells, and capable to form tumor in vivo. Thus, SNP rs7928736 of LUZP2 may be a marker for screening COPD with high risk of lung cancer, and LUZP2 may be a potential target for gene therapy to reduce the risk of COPD patients to develop lung cancer.
Author Block: L. Zhao1, M. d. Andrade2, J. Na2, J. A. Wampfler2, M. Zhang3, A. H. Limper4, P. Yang3; 1Department of Respiratory disease, Third Affiliated Hospital of Second Military Medical University, Shanghai, China, 2Division of Biomedical Statistics and Informatics, Mayo clinic, Rochester, MN, United States, 3Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN, United States, 4Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States.
Rationale: Chronic obstructive pulmonary disease (COPD) is a known risk factor for lung cancer; the morbidity and mortality of lung cancer in COPD is obviously higher than each disease alone. In order to find the genomic relationship between COPD and lung cancer, we conducted a genomic validation-functional confirmation study to test highly-selected single nucleotide polymorphisms (SNPs) which have been previously screened as candidate in promoting COPD to Lung cancer. Methods: We tested 217 SNPs from our previous study in 2484 individuals from Mayo Clinic and LTRC (Lung Tissue Research Consortium) in four models: lung cancer VS control, COPD VS control, lung cancer with COPD VS control, and lung cancer with COPD VS COPD. We evaluated the relevance to tumor of the gene containing the significant SNPs and their biological functions. Results: A SNP (rs7928736) in LUZP2 gene was validated to be associated with progression from COPD to lung cancer (LUZP2), OR=1.80 and P=1.58×10-3. The basic research data indicate that both transcription level and protein level of LUZP2 were higher in NSCLC tissues and cells than in adjacent non-cancerous tissues and normal lung endothelial cells. The mechanism study shows that knockdown of LUZP2 by a lentiviral approach inhibited the proliferation and invasion in H1650, A549 and NCI-H1299 cells, and caused G1 arrest. In addition, in-vivo tumor bearing experiments show that LUZP2 depletion suppressed the growth of NSCLC tumors. Conclusions: LUZP2 may be a key gene for COPD patients to develop NSCLC, and its high expression in lung cancer tissue or cells, which is associated with SNP rs7928736. Knockdown of LUZP2 suppressed the proliferation and invasion in NSCLC cells, and capable to form tumor in vivo. Thus, SNP rs7928736 of LUZP2 may be a marker for screening COPD with high risk of lung cancer, and LUZP2 may be a potential target for gene therapy to reduce the risk of COPD patients to develop lung cancer.
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