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.
Highlights
(NSCLC), a large proportion of patients die from disease recurrence
ENO1 rs2274971A >G and PFKM rs11168417C >T were significantly associated with overall survival (OS) and disease-free survival (DFS)
Three single nucleotide polymorphisms (SNPs) (ENO1 rs2274971A >G, PFKM rs11168417C >T, and PDK2 rs3785921G >A) were significantly associated with OS and/or DFS in squamous cell carcinoma (SCC) but not in adenocarcinoma (AC), whereas PFKP rs1132173C >T exhibited a significant association with survival outcomes in AC but not in SCC (Table 3 and Supplementary Figure 1A–D)
Summary
(NSCLC), a large proportion of patients die from disease recurrence. Pathologic stage is the most important predictor of prognosis after surgical resection of NSCLC. The increased glucose uptake in cancer cells compared to in normal cells is widely exploited in positron emission tomography imaging using 18F-fluorodeoxyglucose (18F-FDG) The major oncogenes such as RAS, MYC, and HIF-1α are key inducers of glycolysis and glucose transporters, whereas tumor suppressor TP53 is known to suppress glycolytic flux[5,6]. We hypothesized that polymorphisms of genes involved in glycolysis affect energy production, macromolecular biosynthesis and other non-glycolytic functions in cancer cells, playing a role in determining the prognosis of patients with lung cancer. To test this hypothesis, we evaluated the association of genetic variants in the glycolytic pathway with the prognosis of lung cancer patients undergoing surgical resection
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