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Annals of surgical oncology, 2019. 26(11), 3756-3764, DOI: https://doi.org/10.1245/s10434-019-07614-2
Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery.
Jang Hyuck Lee, Shin KM;Lee SY;Hong MJ;Choi JE;Kang HG;Do SK;Lee WK;Lee EB;Seok Y;Jeong JY;Yoo SS;Lee J;Cha SI;Kim CH;Cho S;Jheon S;Kim YC;Oh IJ;Na KJ;Kim MS;Lee JM;Yang HC;Jung CY;Park CK;Lee MK;Kim DK;Park JY
Background. We evaluated the association betweengenetic variants in the Notch pathway and survival outcomesof patients with surgically resected NSCLC.
Methods. Sixty-four single nucleotide polymorphisms(SNPs) in the Notch pathway genes were evaluated in thediscovery study (n = 354) and two sequential validationstudies (n = 772 and n = 746, respectively). The associationof genotype with overall survival (OS) and diseasefreesurvival (DFS) was evaluated.
Results. Of the 64 SNPs analyzed in the discovery study, 9were significantly associated with OS or DFS. Amongthem, the association remained significant only for Deltex-1 (DTX1) rs1732786A[G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A[G and survival outcomes. Inthe combined analysis, rs1732786A[G was significantlyassociated with better OS and DFS (adjusted HR aHR forOS, 0.75; 95% CI 0.64–0.87; P = 0.0002; aHR for DFS,0.79; 95% CI 0.71–0.89; P = 0.0001). In vitro luciferaseassay showed that the rs1732786G allele was associatedwith higher promoter activity compared to rs1732786Aallele. Consistently, relative mRNA expression level ofDTX1 showed significant positive correlation withrs1732786 A-to-G change (Ptrend = 0.02) in tumor tissues.
Conclusions. These results suggest that DTX1 rs1732786is a potential prognostic factor that may have clinical utilityin the management of early stage NSCLC.
- DOI: https://doi.org/10.1245/s10434-019-07614-2
- ISBN or ISSN: 1068-9265
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- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.