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Sci Rep. 2016 Oct 21;6:35603. doi: 10.1038/srep35603.

Genetic polymorphisms in glycolytic pathway are associated with the prognosis of patients with early stage non-small cell lung cancer.

Lee SY1,2, Jin CC3,4, Choi JE3,5, Hong MJ3,4, Jung DK3,4, Do SK3,4, Baek SA3, Kang HJ3, Kang HG3,5, Choi SH2, Lee WK6, Seok Y1,7, Lee EB1,7, Jeong JY8, Shin KM9, Cho S10, Yoo SS1,2, Lee J2, Cha SI2, Kim CH2, Lee YM11, Lee IK2, Jheon S10, Park JY1,2,3,4,5.

Author information

1
Lung Cancer Center, Kyungpook National University Medical Center, Daegu 41404, Republic of Korea.
2
Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
3
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
4
BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu 41944, Republic of Korea.
5
Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
6
Biostatistics Center, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
7
Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
8
Department of Pathology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
9
Department of Radiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
10
Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul 13620, Republic of Korea.
11
College of Pharmacy, Kyungpook National University, Daegu, 41566, Republic of Korea.

Abstract

This study was conducted to investigate whether polymorphisms of genes involved in glycolysis are associated with the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Forty-four single nucleotide polymorphisms (SNPs) of 17 genes in glycolytic pathway were investigated in a total of 782 patients with NSCLC who underwent curative surgical resection. The association of the SNPs with overall survival (OS) and disease free survival (DFS) were analyzed. Among the 44 SNPs investigated, four SNPs (ENO1 rs2274971A > G, PFKM rs11168417C > T, PFKP rs1132173C > T, PDK2 rs3785921G > A) were significantly associated with survival outcomes in multivariate analyses. When stratified by tumor histology, three SNPs (ENO1 rs2274971A > G, PFKM rs11168417C > T, and PDK2 rs3785921G > A) were significantly associated with OS and/or DFS only in squamous cell carcinoma, whereas PFKP rs1132173C > T exhibited a significant association with survival outcomes only in adenocarcinoma. When the four SNPs were combined, OS and DFS decreased as the number of bad genotypes increased (Ptrend = 8 × 10-4 and 3 × 10-5, respectively). Promoter assays showed that ENO1 rs2274971G allele had significantly higher promoter activity compared to the rs2274971A allele. The four SNPs, especially ENO1 rs2274971A > G, may be useful for the prediction of prognosis in patients with surgically resected NSCLC.

PMID:
27767175
PMCID:
PMC5073284
DOI:
10.1038/srep35603
[Indexed for MEDLINE]
Free PMC Article

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