[Up-regulation of DLK1 in non-small cell lung cancer and the relevant molecular mechanism]

Zhonghua Zhong Liu Za Zhi. 2016 Jul;38(7):510-4. doi: 10.3760/cma.j.issn.0253-3766.2016.07.006.
[Article in Chinese]

Abstract

Objective: To explore the expression of delta-like 1 homolog (DLK1) gene in non-small cell lung cancer (NSCLC) and its regulatory mechanism.

Methods: The expression levels of DLK1 protein in 204 NSCLC tissues were examined by immunohistochemical (IHC) staining, and the correlation between DLK1expression and clinicopathological features was analyzed. Bisulfate sequencing PCR (BSP) of DNA samples from the tumor tissues of 18 NSCLC patients was performed to evaluate the DNA methylation status of CpG island in the DLK1 promoter region, and also compared with the corresponding IHC staining of DLK1 protein in the same samples.

Results: Among the 102 squamous cell carcinoma (SCC) tissue specimens and their adjacent normal bronchial epithelia, DLK1 was up-regulated in 72 and 37 samples, respectively (P=0.001), and among 102 adenocarcinomas (ADC) tissues and their adjacent alveolar tissues, DLK1 was up-regulated in 77 and 7 samples, respectively (P<0.001). In addition, overexpression of DLK1 was significantly associated with histological type, clinical stage and tumor size of NSCLC (P<0.05 for all). The expression of DLK1protein was inversely correlated with its promoter methylation (P<0.05).

Conclusion: DLK1 expression is up-regulated in NSCLCs, which may be due, at least in part, to the DNA hypomethylation in the promoter region of theDLK1 gene.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Calcium-Binding Proteins
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • CpG Islands
  • DNA Methylation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / metabolism*
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Tumor Burden
  • Up-Regulation

Substances

  • Calcium-Binding Proteins
  • DLK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neoplasm Proteins