Cell-Free DNA Concentration in Pleural Fluid and Serum: Quantitative Approach and Potential Prognostic Factor in Patients with Cancer and Pleural Effusions

Benlloch, Susana; Martí-Ciriquián, Juan Luis; Galbis-Caravajal, José M.; Martín, César Casquet; Sánchez‐Paya, José; Rodríguez-Paniagua, José Manuel; Romero, Santiago; Massutí, Bartomeu

doi:10.3816/clc.2006.n.043

Cited by 21 publications

(20 citation statements)

References 14 publications

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“…An increase in the levels of EC DNA in plasma accompanies a number of pathological states (12), including cancer (13), myocardial infarction (14), stroke (15,16), and trauma (17). Increased levels of EC DNA also serve as a predictor of the severity and clinical outcome in sepsis (18,19), pulmonary emboli (20,21), and exudative pleural injury (22,23) as well as the mortality of critically ill patients in intensive care units (24,25).…”

mentioning

confidence: 99%

Effects of Extracellular DNA on Plasminogen Activation and Fibrinolysis

Komissarov¹,

Florova²,

Idell³

2011

Journal of Biological Chemistry

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Background: Elevated levels of extracellular DNA and aberrant fibrinolysis occur in a range of severe diseases. Results: DNA competes with fibrin for fibrinolytic enzymes. DNA stimulates fibrin-independent plasminogen activation and increases enzyme susceptibility to serpins. Conclusion: DNA is a macromolecular template that both potentiates and inhibits fibrinolysis. Significance: Understanding the interaction of DNA with the fibrinolytic system could improve the outcomes of fibrinolytic therapy.

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confidence: 99%

Effects of Extracellular DNA on Plasminogen Activation and Fibrinolysis

Komissarov¹,

Florova²,

Idell³

2011

Journal of Biological Chemistry

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“…Hence we used matched serum as a reference comparator to pleural fluid in evaluating the utility of cfDNA and DNA integrity index in diagnosing malignancy. An alternative approach to distinguish malignant from benign effusions has been to evaluate the utility of quantitative and qualitative tumour-specific alterations, such as microsatellite alterations in effusion DNA [24-28]. Economidou et al studied patients with malignant (n=26) and benign (n=22) effusions and found that microsatellite instability and loss of heterozygosity in DNA from pleural fluid and blood were not diagnostically useful [27].…”

Section: Discussionmentioning

confidence: 99%

“…Economidou et al studied patients with malignant (n=26) and benign (n=22) effusions and found that microsatellite instability and loss of heterozygosity in DNA from pleural fluid and blood were not diagnostically useful [27]. Conversely, Benlloch et al [24] and Chan et al [25] demonstrated that pleural effusion total DNA was significantly higher in MPE compared to benign effusions. However, in the study by Benlloch et al, all parapneumonic effusions were excluded from analysis and MPEs were compared predominantly to transudate effusions [24].…”

Section: Discussionmentioning

confidence: 99%

Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas

et al. 2012

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BackgroundThe diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE.MethodsWe studied 75 pleural fluid and matched serum samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real-time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified using ELISA.ResultsBased on clinico-pathological evaluation, 52 subjects had MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8; p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and pleural fluid DNA integrity index were considered together, they exhibited 81% sensitivity and 87% specificity in distinguishing benign and malignant effusions. In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated pleural fluid DNA integrity index had an 81% positive predictive value in detecting MPEs. In the detection of mesothelioma, at a specificity of 90%, pleural fluid DNA integrity index had similar sensitivity to pleural fluid and serum mesothelin (75% each respectively).ConclusionPleural fluid DNA integrity index is a promising diagnostic biomarker for identification of MPEs, including mesothelioma. This biomarker may be particularly useful in cases of MPE where pleural aspirate cytology is negative, and could guide the decision to undertake more invasive definitive testing. A prospective validation study is being undertaken to validate our findings and test the clinical utility of this biomarker for altering clinical practice.

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“…In other study of Benlloch et al [9], pleural fluid cfDNA concentration was higher in patients with malignant pleural effusions than in those with effusions caused by other pathologies, but they did not include patients with PPE and the group of benign pleural effusions were mostly transudative.…”

Section: Accepted Manuscriptmentioning

confidence: 94%