Blood Res.  2019 Jun;54(2):114-119. 10.5045/br.2019.54.2.114.

Clinical significance of cell-free DNA as a prognostic biomarker in patients with diffuse large B-cell lymphoma

• Eskandari
• Manoochehrabadi S
• Pashaiefar H
• Zaimy MA
• Ahmadvand

• KMID: 2451011
• DOI: http://doi.org/10.5045/br.2019.54.2.114

Abstract

BACKGROUND
Cell-free DNA (cfDNA) has the potential to serve as a non-invasive prognostic biomarker in some types of neoplasia. The investigation of plasma concentration of cfDNA may reveal its use as a valuable biomarker for risk stratification of diffuse large B-cell lymphoma (DLBCL). The present prognostic value of plasma cfDNA has not been widely confirmed in DLBCL subjects. Here, we evaluated cfDNA plasma concentration and assessed its potential prognostic value as an early DLBCL diagnostic tool.
METHODS
cfDNA concentrations in plasma samples from 40 patients with DLBCL during diagnosis and of 38 normal controls were determined with quantitative polymerase chain reaction (qPCR) for the multi-locus L1PA2 gene.
RESULTS
Statistically significant elevation in plasma cfDNA concentrations was observed in patients with DLBCL as compared to that in normal controls (P<0.05). A cutoff point of 2.071 ng/mL provided 82.5% sensitivity and 62.8% specificity and allowed successful discrimination of patients with DLBCL from normal controls (area under the curve=0.777; P=0.00003). Furthermore, patients with DLBCL showing higher concentrations of cfDNA had shorter overall survival (median, 9 mo; P=0.022) than those with lower cfDNA levels. In addition, elevated cfDNA concentration was significantly associated with age, B-symptoms, International Prognostic Index (IPI) score, and different stages of disease (all P<0.05).
CONCLUSION
Quantification of cfDNA with qPCR at the time of diagnosis may allow identification of patients with high cfDNA concentration, which correlates with aggressive clinical outcomes and adverse prognosis.

Keyword

Cell-free DNA; Biomarker; Prognosis; Quantitative PCR; DLBCL

MeSH Terms

B-Lymphocytes*
Diagnosis
Discrimination (Psychology)
DNA*
Humans
Lymphoma, B-Cell*
Plasma
Polymerase Chain Reaction
Prognosis
Sensitivity and Specificity
DNA

Figure

• 

  Fig. 1 Comparison between patients with DLBCL and normal subjects. Elevated level of cfDNA in patients with DLBCL. qPCR analysis of cfDNA level in the plasma of patients with DLBCL (N=40) and normal controls (N=38) (P<0.05).

• 

  Fig. 2 ROC curve of cfDNA concentration values. cfDNA cutoff value of 2.071 ng/mL (sensitivity 82.5%; specificity 62.8%; 95% CI, 0.674–0.880; AUC=0.777; P<0.00003). An AUC value between 0.7 and 0.8 is considered acceptable.

• 

  Fig. 3 Elevated cfDNA concentration correlates with poor overall survival in patients with DLBCL. Kaplan–Meier analysis of overall survival was evaluated according to cfDNA levels (P=0.043).

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