Kang Hyo Gyoung, Yoo Seung Soo, Choi Jin Eun, Hong Mi Jeong, Do Sook Kyung, Jin Cheng Cheng, Kim Soyoun, Lee Won Kee, Choi Sun Ha, Lee So Yeon, Kim Hyun Jung, Lee Shin Yup, Lee Jaehee, Cha Seung Ick, Kim Chang Ho, Seok Yangki, Lee Eungbae, Cho Sukki, Jheon Sanghoon, Park Jae Yong
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Department of Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Oncotarget. 2017 Jun 27;8(37):61777-61785. doi: 10.18632/oncotarget.18693. eCollection 2017 Sep 22.
This study was conducted to investigate the association between variants in mitotic checkpoint-related genes and clinical outcomes of non-small cell lung cancer (NSCLC). A total of 766 patients with NSCLC who underwent curative surgery were enrolled. Among the 73 variants evaluated, 4 variants were related with survival outcomes. rs7897156C>T was associated with worse overall survival under a recessive model (adjusted hazard ratio = 1.58, 95% confidence interval = 1.07-2.33, = 0.02). rs1059476G>A was associated with better overall survival under a recessive model (adjusted hazard ratio = 0.64, 95% confidence interval = 0.41-0.99, = 0.05). rs1895320T>C and rs1374297C>G were associated with worse disease-free survival. In the functional study, relative luciferase activity was higher at the rs7897156T allele compared to that at the C allele. Western blot showed that the phosphorylation of AKT and mTOR in the variant-type (M) was significantly lower than in the wild-type (T). We found that 4 variants of mitotic checkpoint-related genes were associated with survival outcomes in patients with surgically resected NSCLC. Particularly, our results suggest that rs7897156C>T and rs1059476G>A are functional variants.
