RACK1 is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer

Yi Young Choi, Shin Yup Lee, Won Kee Lee, Hyo Sung Jeon, Eung Bae Lee, Hyun Cheol Lee, Jin Eun Choi, Hyo Gyoung Kang, Eun Jin Lee, Eun Young Bae, Seung Soo Yoo, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, In-San Kim, Myung Hoon Lee, Young Tae Kim, Sanghoon Jheon, Jae Yong Park

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4451-4466
Number of pages16
JournalOncotarget
Volume6
Issue number6
DOIs
Publication statusPublished - 2015 Jan 1
Externally publishedYes

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Non-Small Cell Lung Carcinoma
Disease-Free Survival
Single Nucleotide Polymorphism
Survival
Genes
Electrophoretic Mobility Shift Assay
Genetic Polymorphisms
Carcinogenesis
Transcription Factors
Multivariate Analysis

Keywords

  • Lung cancer
  • Polymorphism
  • RACK1
  • Survival

ASJC Scopus subject areas

  • Oncology

Cite this

Choi, Y. Y., Lee, S. Y., Lee, W. K., Jeon, H. S., Lee, E. B., Lee, H. C., ... Park, J. Y. (2015). RACK1 is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer. Oncotarget, 6(6), 4451-4466. https://doi.org/10.18632/oncotarget.2865

RACK1 is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer. / Choi, Yi Young; Lee, Shin Yup; Lee, Won Kee; Jeon, Hyo Sung; Lee, Eung Bae; Lee, Hyun Cheol; Choi, Jin Eun; Kang, Hyo Gyoung; Lee, Eun Jin; Bae, Eun Young; Yoo, Seung Soo; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Kim, In-San; Lee, Myung Hoon; Kim, Young Tae; Jheon, Sanghoon; Park, Jae Yong.

In: Oncotarget, Vol. 6, No. 6, 01.01.2015, p. 4451-4466.

Research output: Contribution to journalArticle

Choi, YY, Lee, SY, Lee, WK, Jeon, HS, Lee, EB, Lee, HC, Choi, JE, Kang, HG, Lee, EJ, Bae, EY, Yoo, SS, Lee, J, Cha, SI, Kim, CH, Kim, I-S, Lee, MH, Kim, YT, Jheon, S & Park, JY 2015, 'RACK1 is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer', Oncotarget, vol. 6, no. 6, pp. 4451-4466. https://doi.org/10.18632/oncotarget.2865
Choi, Yi Young ; Lee, Shin Yup ; Lee, Won Kee ; Jeon, Hyo Sung ; Lee, Eung Bae ; Lee, Hyun Cheol ; Choi, Jin Eun ; Kang, Hyo Gyoung ; Lee, Eun Jin ; Bae, Eun Young ; Yoo, Seung Soo ; Lee, Jaehee ; Cha, Seung Ick ; Kim, Chang Ho ; Kim, In-San ; Lee, Myung Hoon ; Kim, Young Tae ; Jheon, Sanghoon ; Park, Jae Yong. / RACK1 is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer. In: Oncotarget. 2015 ; Vol. 6, No. 6. pp. 4451-4466.
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AU - Choi, Yi Young

AU - Lee, Shin Yup

AU - Lee, Won Kee

AU - Jeon, Hyo Sung

AU - Lee, Eung Bae

AU - Lee, Hyun Cheol

AU - Choi, Jin Eun

AU - Kang, Hyo Gyoung

AU - Lee, Eun Jin

AU - Bae, Eun Young

AU - Yoo, Seung Soo

AU - Lee, Jaehee

AU - Cha, Seung Ick

AU - Kim, Chang Ho

AU - Kim, In-San

AU - Lee, Myung Hoon

AU - Kim, Young Tae

AU - Jheon, Sanghoon

AU - Park, Jae Yong

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Lung cancer

KW - Polymorphism

KW - RACK1

KW - Survival

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