RACK1is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer

// Yi-Young Choi 1, * , Shin Yup Lee 2, 3, * , Won Kee Lee 4, * , Hyo-Sung Jeon 1, 3, * , Eung Bae Lee 3, 5 , Hyun Cheol Lee 6 , Jin Eun Choi 1, 3 , Hyo-Gyoung Kang 1 , Eun Jin Lee 3 , Eun Young Bae 1 , Seung Soo Yoo 2, 3 , Jaehee Lee 2 , Seung Ick Cha 2 , Chang Ho Kim 2 , In-San Kim 1 , Myung Hoon Lee 6 , Young Tae Kim 7 , Sanghoon Jheon 7 , Jae Yong Park 1, 2, 3 1 Departments of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea 2 Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea 3 Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea 4 Biostatistics Center, School of Medicine, Kyungpook National University, Daegu, Republic of Korea 5 Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea 6 Diagnosis and Prediction Biotechnology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea 7 Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea * These authors have contributed equally to this work Correspondence to: Jae Yong Park, e-mail: jaeyong@knu.ac.kr Sanghoon Jheon, e-mail: jheon@snubh.org Keywords: polymorphism, RACK1, lung cancer, survival Received: August 28, 2014      Accepted: December 07, 2014      Published: January 08, 2015 ABSTRACT Background: This study was conducted to identify genetic polymorphisms associated with the prognosis of patients with early stage NSCLC. Materials and Methods: We genotyped 1,969 potentially functional single nucleotide polymorphisms (SNPs) of 1,151 genes involved in carcinogenesis in 166 NSCLC patients who underwent curative surgery, using the Affymetrix custom-made GeneChip. A replication study was performed in an independent cohort of 626 patients. Results: Fifty six SNPs which were associated with both overall survival (OS) and disease-free survival (DFS) with log-rank P values < 0.05 in discovery set were selected for validation. Among those, five SNPs ( RACK1 rs1279736C>A and rs3756585T>G, C3 rs2287845T>C, PCAF rs17006625A>G, and PCM1 rs17691523C>G) were found to be significantly associated with survival in the same direction as the discovery set. In combined analysis, the rs1279736C>A and rs3756585T>G were most significantly associated with OS and DFS in multivariate analysis ( P for OS = 4 × 10 −5 and 7 × 10 −5 , respectively; and P for DFS = 0.003, both; under codominant model). In vitro promoter assay and electrophoretic mobility shift assay revealed that the rs3756585 T-to-G change increased promoter activity and transcription factor binding of RACK1 . Conclusions: We identified five SNPs, especially RACK1 rs3756585T>G, as markers for prognosis of patients with surgically resected NSCLC.