Blood Res  
Clinical significance of cell-free DNA as a prognostic biomarker in patients with diffuse large B-cell lymphoma
Mahsa Eskandari1, Saba Manoochehrabadi2, Hossein Pashaiefar3,4, Mohammad Ali zaimy5, Mohammad Ahmadvand3,4
1Pharmaceutical Sciences Branch, Islamic Azad University, 2Medical Genetics, Department of Medical Genetics,
Faculty of Medicine, Shahid Beheshti University of Medical Sciences, 3Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, 4Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Hematologic Malignancies Research Center, Tehran University of Medical Sciences, Tehran, 5Department of Medical Genetics, Faculty of Medicine, Ilam
University of Medical Sciences, Ilam, Iran
Correspondence to: Mohammad Ahmadvand, Ph.D.
Tehran University of Medical Science, Tehran, Iran
E-mail: mahmadvand@sina.tums.ac.ir
Published online: April 11, 2019.
© The Korean Journal of Hematology. All rights reserved.

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 sex, B-symptoms, and different stages of disease (all P<0.05).
Conclusions: 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
Keywords: Cell-free DNA, Biomarker, Prognosis, Quantitative PCR, DLBCL


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