Oncotarget

Research Papers:

Polymorphisms in mitotic checkpoint-related genes can influence survival outcomes of early-stage non-small cell lung cancer

Hyo Gyoung Kang, Seung Soo Yoo, Jin Eun Choi, Mi Jeong Hong, Sook Kyung Do, Cheng Cheng Jin, Soyoun Kim, Won Kee Lee, Sun Ha Choi, So Yeon Lee, Hyun Jung Kim, Shin Yup Lee, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Yangki Seok, Eungbae Lee, Sukki Cho, Sanghoon Jheon and Jae Yong Park _

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Oncotarget. 2017; 8:61777-61785. https://doi.org/10.18632/oncotarget.18693

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Abstract

Hyo Gyoung Kang1,2,*, Seung Soo Yoo3,*, Jin Eun Choi1,2, Mi Jeong Hong1,2, Sook Kyung Do1,4, Cheng Cheng Jin1, Soyoun Kim1, Won Kee Lee5, Sun Ha Choi3, So Yeon Lee3, Hyun Jung Kim3, Shin Yup Lee3, Jaehee Lee3, Seung Ick Cha3, Chang Ho Kim3, Yangki Seok6, Eungbae Lee6, Sukki Cho7, Sanghoon Jheon7 and Jae Yong Park1,2,3,4

1Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

2Department of Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

3Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

4BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea

5Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

6Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

7Department of Thoracic and Cardiovascular Surgery, School of Medicine, Seoul National University, Seoul, Republic of Korea

*These authors have contributed equally to this paper

Correspondence to:

Jae Yong Park, email: jaeyong@knu.ac.kr

Keywords: polymorphisms, mitosis, mitotic checkpoint, survival outcome, lung cancer

Received: December 02, 2016    Accepted: May 22, 2017    Published: June 27, 2017

ABSTRACT

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. BUB3 rs7897156C>T was associated with worse overall survival under a recessive model (adjusted hazard ratio = 1.58, 95% confidence interval = 1.07–2.33, P = 0.02). AURKB rs1059476G>A was associated with better overall survival under a recessive model (adjusted hazard ratio = 0.64, 95% confidence interval = 0.41–0.99, P = 0.05). PTTG1 rs1895320T>C and RAD21 rs1374297C>G were associated with worse disease-free survival. In the functional study, relative luciferase activity was higher at the BUB3 rs7897156T allele compared to that at the C allele. Western blot showed that the phosphorylation of AKT and mTOR in the AURKB variant-type (M298) was significantly lower than in the AURKB wild-type (T298). 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 BUB3 rs7897156C>T and AURKB rs1059476G>A are functional variants.


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