Clinical Research Papers:
RACK1 is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer
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Yi-Young Choi1,*, Shin Yup Lee2,3,*, Won Kee Lee4,*, Hyo-Sung Jeon1,3,*, Eung Bae Lee3,5, Hyun Cheol Lee6, Jin Eun Choi1,3, Hyo-Gyoung Kang1, Eun Jin Lee3, Eun Young Bae1, Seung Soo Yoo2,3, Jaehee Lee2, Seung Ick Cha2, Chang Ho Kim2, In-San Kim1, Myung Hoon Lee6, Young Tae Kim7, Sanghoon Jheon7, Jae Yong Park1,2,3
1Departments of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea
2Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
3Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea
4Biostatistics Center, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
5Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
6Diagnosis and Prediction Biotechnology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
7Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea
*These authors have contributed equally to this work
Jae Yong Park, e-mail: [email protected]
Sanghoon Jheon, e-mail: [email protected]
Keywords: polymorphism, RACK1, lung cancer, survival
Received: August 28, 2014 Accepted: December 07, 2014 Published: January 08, 2015
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.
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