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- Title
Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer.
- Authors
Kang, Hyo-Gyoung; Park, Ji Eun; Lee, Shin Yup; Choi, Jin Eun; Do, Sook Kyung; Hong, Mi Jeong; Lee, Jang Hyuck; Jeong, Ji Yun; Do, Young Woo; Lee, Eung Bae; Shin, Kyung Min; Lee, Won Ki; Choi, Sun Ha; Lee, Yong Hoon; Seo, Hye won; Yoo, Seung Soo; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Cho, Sukki
- Abstract
Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.
- Subjects
LUNG cancer prognosis; LUNG cancer; ADENOCARCINOMA; EPITHELIAL cell tumors; CONFIDENCE intervals; SINGLE nucleotide polymorphisms; GENETIC polymorphisms; ALLELES; RNA; CANCER patients; GENE expression; DESCRIPTIVE statistics; SURVIVAL analysis (Biometry); GENOTYPES; TRANSCRIPTION factors
- Publication
Oncology, 2021, Vol 99, Issue 5, p336
- ISSN
0030-2414
- Publication type
Article
- DOI
10.1159/000514131