An inverse correlation between Interleukin-6 and select gene promoter methylation in patients with gastric cancer

Digestion. 2006;74(2):85-90. doi: 10.1159/000097623. Epub 2006 Nov 30.

Abstract

Background: Both serum IL-6 levels and CpG island methylation have been shown to have prognostic significance in gastric cancer, it was suggested that an important link existed between IL-6 and methylation of cancers.

Aim: To investigate the prognostic value of IL-6 serum level and the association between serum IL-6 levels and CpG island methylation at p16, DAPK, MGMT and E-cadherin in patients with gastric cancer.

Patients and methods: Methylation status was assessed by MSP in 75 surgical specimens of gastric adenocarcinoma. IL-6 serum levels were measured by chemiluminescent enzyme immunoassay (CLEIA).

Results: Methylation of p16, DAPK, MGMT, and E-cadherin were present in 53, 48, 32, and 59% of patients. Patients with tumors methylated at p16 and DAPK had lower serum levels of IL-6 compared to unmethylated tumors (1.8 vs. 4.8 pg/ml, p = 0.01 for p16; 1.5 vs. 6.2 pg/ml, p = 0.0001 for DAPK). But there was no difference with MGMT and E-cadherin methylation status. Serum IL-6 levels were also associated with TNM stage (p = 0.001), depth of tumor invasion (p = 0.002), lymphatic invasion (p = 0.01), vascular invasion (p = 0.008), metastasis (p = 0.002) and signet cell histology (p = 0.001).

Conclusion: IL-6 is of prognostic value for patients of gastric cancer. Low serum IL-6 levels were associated with p16 or DAPK gene methylation in patients with gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins / genetics
  • Cadherins / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • CpG Islands / genetics
  • DNA Methylation*
  • DNA Modification Methylases
  • DNA Repair Enzymes
  • Death-Associated Protein Kinases
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor*
  • Genes, p16
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Tumor Suppressor Protein p14ARF / genetics
  • Tumor Suppressor Proteins

Substances

  • Apoptosis Regulatory Proteins
  • Cadherins
  • Interleukin-6
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • DNA Repair Enzymes