Effect of genetic variation in Notch regulator DTX1 on SCLC prognosis compared with the effect on NSCLC prongosis

Thorac Cancer. 2020 Sep;11(9):2698-2703. doi: 10.1111/1759-7714.13566. Epub 2020 Jul 22.

Abstract

Deltex-1 (DTX1) is a negative regulator of the Notch signaling pathway. Here, we investigated the clinical effect of DTX1 rs1732786A > G, which is associated with better prognosis in patients with early-stage non-small cell lung cancer (NSCLC), in 261 patients with small cell lung cancer (SCLC). DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in the codominant model (odds ratio = 0.42, 95% confidence interval [CI]: 0.26-0.66, P = 2 × 10-4 ; hazard ratio = 1.47, 95% CI: 1.17-1.84, P = 0.001, respectively). An in vitro luciferase assay was performed, and the 1732786G allele demonstrated significantly higher promoter activity than the 1732786A allele (P = 2 × 10-7 ). In summary, DTX1 rs1732786A > G was associated with poor prognosis in patients with SCLC as opposed to patients with NSCLC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: DTX1 rs1732786A > G was associated with better prognosis in patients with early-stage non-small cell lung cancer (NSCLC) in our previous study. WHAT THIS STUDY ADDS: DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer (SCLC).

Keywords: DTX1; SCLC; response; rs1732786; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Genotype
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Notch / genetics*
  • Receptors, Notch / metabolism
  • Signal Transduction
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / metabolism
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology
  • Survival Analysis
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Receptors, Notch
  • DTX1 protein, human
  • Ubiquitin-Protein Ligases