Assessment of the circulating cell-free DNA marker association with diagnosis and prognostic prediction in patients with lymphoma: a single-center experience

Ann Hematol. 2017 Aug;96(8):1343-1351. doi: 10.1007/s00277-017-3043-5. Epub 2017 Jun 16.

Abstract

Circulating cell-free DNA (ccfDNA) has been shown to be associated with the clinical characteristics and prognosis of cancer patients. Our objective was to assess whether the concentration and integrity index of ccfDNA in plasma may be useful for diagnosing and monitoring the progression of patients with lymphoma. We included plasma samples from 174 lymphoma patients and 80 healthy individuals. The total concentration of ccfDNA was determined using a fluorometry method, and the DNA integrity index (DII), which is the ratio of longer to shorter DNA fragments, for the APP gene was detected using real-time quantitative PCR. The median levels of the ccfDNA concentration and the DII in patients with lymphoma were significantly higher than those in controls (both P < 0.0001). Increases in the ccfDNA concentration and the DII were associated with advanced stage disease, elevated lactate dehydrogenase levels, and a higher prognosis score. In patients with diffuse large B cell lymphoma (DLBCL), high levels of ccfDNA (both concentration and the DII) showed an inferior 2-year progression-free survival (PFS) (P = 0.001; P < 0.0001, respectively). Our study provides quantitative and qualitative evidence in favor of using ccfDNA analysis in lymphoma patients for diagnostic and prognostic assessments.

Keywords: Circulating DNA; Integrity; Lymphoma; Prognosis.

MeSH terms

  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / genetics*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma / blood
  • Lymphoma / diagnosis
  • Lymphoma / genetics*
  • Lymphoma, Large B-Cell, Diffuse / blood
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Real-Time Polymerase Chain Reaction / statistics & numerical data

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm