Circulating cell-free DNA as a prognostic and predictive biomarker in non-small cell lung cancer

Oncotarget. 2016 Jul 12;7(28):44583-44595. doi: 10.18632/oncotarget.10069.

Abstract

Circulating cell-free DNA (cfDNA), which can be obtained from plasma or serum by non-invasive procedures, has showed great potential to predict treatment response and survival for cancer patients. Several studies have assessed the prognostic and predictive value of cfDNA in non-small cell lung cancer (NSCLC). However, these studies were often small and reported varying results. To address this issue, a meta-analysis was carried out. A total of 22 studies involving 2518 patients were subjected to the final analysis. Our results indicated that NSCLC patients with higher cfDNA concentration had shorter median progression-free survival (PFS) and overall survival (OS) time. In addition, high levels of cfDNA were significantly associated with poor PFS (hazard ratio or HR, 1.32; 95% CI, 1.02-1.71) and OS (HR, 1.64; 95% CI, 1.26-2.15). With respect to tumor specific mutations, we failed to reveal significant differences for PFS (HR, 1.30; 95% CI, 0.66-2.56) and OS (HR, 1.05; 95% CI, 0.49-2.25) when NSCLC patients were grouped according to KRAS genotype detected in cfDNA. However, NSCLC patients which harbored EGFR activating mutation in cfDNA had a greater chance of response to EGFR-TKIs (odds ratio or OR, 1.96; 95% CI, 1.59-2.42). No significant publication bias was detected in this study. In conclusion, cfDNA could act as a prognostic and predictive biomarker for patients with NSCLC.

Keywords: biomarker; circulating cell-free DNA; meta-analysis; non-small cell lung cancer; prognosis.

Publication types

  • Meta-Analysis

MeSH terms

  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell-Free Nucleic Acids / blood
  • Cell-Free Nucleic Acids / genetics*
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / genetics*
  • Disease-Free Survival
  • ErbB Receptors / genetics
  • Genotype
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Mutation
  • Outcome Assessment, Health Care
  • Predictive Value of Tests
  • Prognosis
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins p21(ras) / genetics

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • DNA, Neoplasm
  • KRAS protein, human
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)