WCIM 2014 SEOUL KOREA 457
Poster Session
The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expres- sion level of KRT81 in tumor tissues.
Conclusions: The rs3660G>C affects KRT81 expression and thus infl uences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.
PS 1598 Lung Cancer
A Panel of Genetic Polymorphism for the Prediction of Prognosis in Patients with Early Stage Non-Small Cell Lung Cancer After Surgical Resection
Shin Yup Lee1, Jin Eun Choi2, Hyo-Sung Jeon2, Yi Young Choi2, Hyo-Gyoung Kang2, Won Kee Lee3, Hyun Cheol Lee4, Myung Hoon Lee4, Seung Soo Yoo1, Jaehee Lee1, Eung Bae Lee5, Seung Ick Cha1, Chang Ho Kim1, Young Tae Kim6, Sanghoon Jheon6, Jae Yong Park1
Department of Internal Medicine, School of Medicine, Kyungpook National University, Korea1, Depart- ment of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Korea2, Biostatistics Center, School of Medicine, Kyungpook National University, Korea3, Diagnosis and Predic- tion Biotechnology, School of Medicine, Kyungpook National University, Korea4, Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Korea5, Department of Thoracic and Car- diovascular Surgery, School of Medicine, Seoul National University, Korea6
Background: This study was conducted to investigate whether a panel of 8 genetic polymorphisms can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection.
Methods: We selected 8 single nucleotide polymorphisms (SNPs) which have been shown to be associated with the prognosis of lung cancer patients after surgery in our previous studies. A total of 814 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the 8 SNPs with overall survival (OS) and disease-free survival (DFS) was analyzed.
Results: Among the 8 SNPs, seven (CD3D rs3181259, CD3EAP rs967591, TNFRSF10B rs1047266, AKT1 rs3803300, C3 rs2287845, GNB2L1 rs3756585, and ADAMTSL3 rs11259927) were significantly associated with OS and DFS, but CASP7 rs2227310 was not signifi cantly associated with either OS or DFS. Combining those 8 SNPs, we designed a prognostic index to predict the prognosis of patients. According to relative risk of death, a score value was assigned to each genotype of the SNPs. For codomi- nant model, 1 for low risk genotype, 2 for intermediate risk genotype, and 3 for high risk genotype were assigned and for dominant and recessive model, 1 for low risk genotype, and 3 for high risk genotype. When we categorized the patients into two
groups based on the prognostic index, high risk group was signifi cantly associated with worse OS and DFS compared to low risk group (aHR for OS = 2.15, 95% CI = 1.64-2.81, P = 2.1 x 10-8, and aHR for DFS = 1.58, 95% CI = 1.29-1.95, P = 1.3 x 10-5).
Conclusions: Prognostic index using 8 genetic polymorphisms may be useful for the prognostication of patients with surgically resected NSCLC.
PS 1599 Lung Cancer
Role of Cyclic AMP Response Element-Binding Protein in Cancer Cells in Response to Glucose Stress
Shin Myung Kang1, Yu Jin Kim1, Sun Young Kyung1, Jeong-Woong Park1, Sung Hwan Jeong1, Se Kyu Kim2, Joon Chang2
Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Hospital, Korea1, Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Korea2 Background: cyclic AMP response element-binding protein (CREB) mediates energy homeostasis and promotes stress resistance in non-cancerous tissues, which is similar to active reprogramming systems of cancer that enable adaptation and survival under environmental metabolic stress. This study was conducted to characterize the role of CREB in cancer cells in response to glucose starvation and investigate differentially expressed genes under glucose deprivation conditions.
Methods: Several human cancer cell lines were used in this study. Transient transfection with siRNA, proliferation assays, and cell viability assays under normal culture conditions or glucose deprivation conditions were performed to explore the metabolic phenotype of CREB. To investigate cell death mode, assessment of poly(ADP-ribose) polymerase (PARP) cleavage by Western blot and an apoptosis assay using a fl ow cytometer were performed.
And the CREB-specifi c gene expression signature under glucose deprivation conditions was investigated by microarray experiments and gene set enrichment analysis.
Results: Expression of phosphorylated CREB was increased under glucose-free me- dia conditions. Proliferation of CREB-knockdown cells was significantly suppressed compared with that of control cells under normal media conditions. The viability of CREB-knockdown cells was signifi cantly higher than that of control ones under meta- bolic stress conditions. Western blot analysis revealed that PARP cleavage induced by glucose deprivation was attenuated by knockdown of CREB. Apoptotic assay revealed that the number of cells undergoing apoptotic death decreased in response to knock- down of CREB under glucose deprivation conditions. CREB-specifi c gene expression signatures under glucose deprivation conditions revealed that energy metabolism-re- lated gene sets such as glycolysis/gluconeogenesis, oxidative phosphorylation, and ATP synthesis were highly enriched.
Conclusions: CREB is essential for cellular proliferation under normal culture media conditions. Under glucose starvation conditions, CREB is activated and mediates apop- totic cell death in correlation with expression of energy metabolism-related gene sets.
