In:
Oncology, S. Karger AG, Vol. 99, No. 5 ( 2021), p. 336-344
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among those SNPs, 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, 〈 i 〉 p 〈 /i 〉 = 0.05), and 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, 〈 i 〉 p 〈 /i 〉 = 0.03). Regarding 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;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 〈 i 〉 HAX1 〈 /i 〉 promoter activity than T allele. 〈 i 〉 HAX1 〈 /i 〉 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, 〈 i 〉 ME3 〈 /i 〉 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G and 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A are associated with the clinical outcomes of patients in surgically resected NSCLC.
Type of Medium:
Online Resource
ISSN:
0030-2414
,
1423-0232
Language:
English
Publisher:
S. Karger AG
Publication Date:
2021
detail.hit.zdb_id:
1483096-6
detail.hit.zdb_id:
250101-6
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