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Original Article

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Blood Res 2019; 54(2):

Published online June 30, 2019

https://doi.org/10.5045/br.2019.54.2.114

© The Korean Society of Hematology

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

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1Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, 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, 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.
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Science, P.O. Box: 1411713135 (M.A.), Tehran, Iran
E-mail: mahmadvand@sina.tums.ac.ir

Received: November 19, 2018; Revised: January 3, 2019; Accepted: January 7, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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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.

Keywords Cell-free DNA, Biomarker, Prognosis, Quantitative PCR, DLBCL

Article

Original Article

Blood Res 2019; 54(2): 114-119

Published online June 30, 2019 https://doi.org/10.5045/br.2019.54.2.114

Copyright © The Korean Society of Hematology.

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

1Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, 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, 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.
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Science, P.O. Box: 1411713135 (M.A.), Tehran, Iran
E-mail: mahmadvand@sina.tums.ac.ir

Received: November 19, 2018; Revised: January 3, 2019; Accepted: January 7, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Cell-free DNA, Biomarker, Prognosis, Quantitative PCR, DLBCL

Fig 1.

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Figure 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).

Blood Research 2019; 54: 114-119https://doi.org/10.5045/br.2019.54.2.114

Fig 2.

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Figure 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.

Blood Research 2019; 54: 114-119https://doi.org/10.5045/br.2019.54.2.114

Fig 3.

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Figure 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).

Blood Research 2019; 54: 114-119https://doi.org/10.5045/br.2019.54.2.114

Table 1 . cfDNA concentrations and clinicopathological characteristics..


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