Methylation Biomarkers of Lung Cancer

A DNA analysis technique called methylation profiling identifies molecular biomarkers in early lung cancer. Biomarkers of lung cancer have been identified by Epigenomics AG with its differential methylation hybridization technology and have been extensively validated on tissue samples before being tested on blood plasma. A large clinical trial has confirmed that a two-biomarker panel correctly identified two-thirds of all lung cancers in blood plasma at a false positive rate of 12% (88% specificity). Most of the blood samples used in the study were obtained from patients with early stage I and II cancer. Sensitivity in stage II lung cancer patients reached 73%. Patients with early stage cancer are significantly underdiagnosed in the current diagnostic practice for lung cancer but could benefit most from early therapeutic intervention.

Despite optimal and early surgical treatment of NSCLC, many patients die of recurrence. This led to investigation of association between gene methylation and recurrence of the tumor. In a multivariate model, the following were associated with tumor recurrence, independently of NSCLC stage, age, sex, race, smoking history, and histologic characteristics of the tumor (Brock et al. 2008):

  • 1. Promoter methylation of the cyclin-dependent kinase inhibitor 2A gene p16;
  • 2. H-cadherin gene CDH13;
  • 3. Ras association domain family 1 gene RASSF1A; and
  • 4. Adenomatous polyposis coli gene APC in tumors and in histologically tumornegative lymph nodes.

It was concluded that methylation of the promoter region of the four genes in patients with stage I NSCLC treated with curative intent by means of surgery is associated with early recurrence.

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