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Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery. | LitMetric

AI Article Synopsis

  • A study investigated the link between genetic variations in the Notch pathway and survival rates in patients with non-small cell lung cancer (NSCLC) who had surgery.
  • Researchers analyzed 64 gene variants in a total of 1,872 patients across multiple studies, identifying 9 variants associated with survival.
  • Specifically, the variant DTX1 rs1732786A>G was consistently associated with improved overall and disease-free survival, indicating its potential as a prognostic factor for NSCLC patients.

Article Abstract

Background: We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC.

Methods: Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated.

Results: Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, 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. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 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 luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (P = 0.02) in tumor tissues.

Conclusions: These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.

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Source
http://dx.doi.org/10.1245/s10434-019-07614-2DOI Listing

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