Cell-free DNA concentration and integrity as a screening tool for cancer

Zaher, Ebtsam R.; Anwar, Medhat Mohamed; Kohail, H.; El-Zoghby, S.M.; Aboeleneen, Marwa S.

doi:10.4103/0019-509x.118721

Cited by 19 publications

(17 citation statements)

References 32 publications

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“…However, there was no statistically significant difference in the level of CEA between COPD and control subjects. This is matched with Zaher et al [23] Stated that CFDNA represented a highly sensitive and specific marker to discriminate cancer patients from control and benign individuals when compared to conventional tumor markers used in various types of cancer diagnosis.…”

Section: Discussionsupporting

confidence: 71%

Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non small cell lung cancer

Soliman

Alhanafy

Habib

et al. 2018

Biochemistry and Biophysics Reports

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BackgroundNon-small cell lung cancer (NSCLC) is leading cause of cancer related death and the survival rate for patients with NSCLC remain poor so early diagnosis of NSCLC represents the best opportunity for cure. Cell-free DNA (cf-DNA) is extracellular nucleic acids found in cell-free plasma/serum of humans, given the recent approval of a liquid biopsy in lung cancer, the use of circulating tumor DNA as a novel non-invasive diagnostic and prognostic biomarker is promising.ObjectivesStudying whether the concentrations of circulating Cell Free DNA in serum can be used as a diagnostic and prognostic biomarker for NSCLC patients.MethodThis study was carried out on 140 subjects included 60 patients with non small cell lung cancer,40 patients with Chronic Obstructive Pulmonary Disease (COPD) and 40 healthy controls. Quantitative analysis of serum circulating cf-DNA was done b y AlU-based quantitative real time PCR. Serum level of CEA was measured by ELISA.ResultsNSCLC patients demonstrated significantly higher values of each of ALU 215, ALU 247, and DNA integrity than both COPD patients and controls. On ROC curve analysis, the total accuracy of ALU 247, ALU 115, DNA integrity (92.1%, 83.6%, 56.4%) at cutoff points (325, 565 & 0.48) respectively. On combining both DNA integrity and CEA, improved sensitivity to 93.3% was noted. For NSCLC patients, ALU 115 & ALU 247 increased significantly with more advanced stage and highest level was noticed in metastatic patients. Regarding survival there was better overall survival among patients with low DNA integrity.ConclusionSerum cf-DNA concentrations and integrity index may be valuable tool in early diagnosis of NSCLC and prediction of prognosis of those patients.

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Section: Discussionsupporting

confidence: 71%

Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non small cell lung cancer

Soliman

Alhanafy

Habib

et al. 2018

Biochemistry and Biophysics Reports

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“…Even though we observed a significant difference in the plasma concentration of ALU115 and ALU247 between benign and malignant thyroid nodules, its clinical utility is limited due to a significant overlap. Although various studies have reported an increase in DNA concentration in cancer patients (22)(23)(24)(25)(26), numerous studies have indicated the limited utility of cfDNA concentration as a biomarker, owing to the wide variations in cfDNA level among the population (11). Moreover, we observed that the concentration difference could be attributed to the size of the lesions since patients with benign lesions were characterized by the larger tumor size, which was associated with the higher ALU115 and ALU247 levels.…”

Section: Discussionmentioning

confidence: 64%

Limited Utility of Circulating Cell-Free DNA Integrity as a Diagnostic Tool for Differentiating Between Malignant and Benign Thyroid Nodules With Indeterminate Cytology (Bethesda Category III)

et al. 2019

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Background: Analysis of plasma circulating cell-free DNA integrity (cfDI) has emerged as a promising tool in the diagnosis of malignant vs. benign tumors. There is limited data on the role of cfDI in thyroid cancer. The goal of this study was to analyze cfDI as a biomarker of malignancy in patients with cytologically indeterminate thyroid nodules. Methods: The cfDI was measured in the plasma of patients with cytologically indeterminate thyroid nodules. All patients underwent plasma collection within 24-72 h before surgical treatment for thyroid nodules. Additionally, samples were collected from seven patients via the vein draining the thyroid and peripheral vein during surgery. Quantitative real-time PCR was performed on the isolated cell-free DNA using two different primer sets (115 and 247 bp) to amplify consensus ALU sequences. The cfDI was calculated as the ratio of ALU247 to ALU115. Results: All data are given as median [25th−75th percentile]. The study group consisted of 67 patients with 100 nodules, 80.6% (54/67) women, aged 43 [33-60] years. There was no difference in cfDI between 29 patients with benign nodules (0.49 [0.41-0.59]) and 38 patients with malignant lesions (0.45 [0.36-0.57], p = 0.19). There was no difference in cfDI in the vein draining the thyroid (0.47 [0.24-1.05]) and peripheral vein (0.48 [0.36-0.56], p = 0.44). In comparison to thyroid cancer patients, patients with benign nodules were characterized by significantly higher concentrations of ALU115 (1,064 [529-2,960] vs. 411 [27-1,049] ng/ml; p = 0.002) and ALU247 (548 [276-1,894] vs. 170 [17-540] ng/ml; p = 0.0005), most likely because benign tumors were larger (3, [1.8-4.1 cm]) than Thakur et al. Liquid Biopsy and Indeterminate Thyroid Nodules malignant lesions (0.7 [0.23-1.45], p < 0.0001). Women had significantly lower cfDI (0.45 [0.27-0.54]) than men (0.56 [0.44-0.8], p = 0.011). Conclusion: The cfDI measured in the vein draining the thyroid is similar to the cfDI measured in the antecubital vein, validating cfDI measurements by peripheral liquid biopsy. Analysis of cfDI needs to be stratified by patients gender. In contrast to its diagnostic utility in aggressive cancers, cfDI has limited utility as a biomarker of malignancy in cytologically indeterminate thyroid nodules.

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“…Although cfDNA levels were not associated with ER or PR, they were significantly higher in HER-2-positive patients than in HER-2-negative patients [ 15 , 28 ]. Most researchers [ 15 , 25 – 28 , 30 – 31 ] showed a higher level of cfDNA in node-positive patients compared to node-negative patients, and as more lymph nodes are involved, more cfDNA could be detected in circulation [ 28 ]. Also, two studies [ 15 , 30 ] reported significant differences in the level of cfDNA between node-positive patients and node-negative patients, which suggested that the concentration of cfDNA might be a possible marker of early lymph node metastasis in breast cancer.…”

Section: Resultsmentioning

confidence: 99%

Quantitation of cell-free DNA in blood is a potential screening and diagnostic maker of breast cancer: a meta-analysis

et al. 2017

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IntroductionIncreased cell-free DNA (cfDNA) levels in circulating blood have been associated with higher possibility of breast cancer, however, researchers have not reached an agreement on its analysis.Materials and MethodsWe conducted a meta-analysis of 12 retrospective studies to clarify the value of cfDNA quantification in screening and diagnosis of breast cancer. PubMed, EMBASE, Web of Science and Cochrane library were searched from January, 2000 to October, 2016. Pooled analyses were estimated using a random effects model.ResultsIn total, 1003 primary breast cancer patients, 283 cases with benign breast disease and 575 healthy individuals were included. Pooled diagnostic odds ratio (DOR) was 27.63 (95% confidence interval [CI]: 10.96~69.61, I2 = 86.2%, P < 0.001) in discriminating between breast cancer and healthy controls; the area under the summary receiver operating characteristic (SROC) curve measured 0.91 (95% CI: 0.17~1.00). Analysis of available data in distinguishing breast cancer and benign breast disease showed a pooled DOR of 35.30 (95% CI: 7.58~164.39, I2 = 79.9%, P = 0.002) with an area under SROC of 0.91 (95% CI: 0.89~0.93). Ethnic group distribution based geographical factors suggested by meta-regression and subgroup analyses explained most of the heterogeneity.ConclusionsQuantification of cfDNA is a promising test in screening and diagnostic of breast cancer, but population-based standardization of test methods require completion prior to clinical use.

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Cell-free DNA concentration and integrity as a screening tool for cancer

Cited by 19 publications

References 32 publications

Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non small cell lung cancer

Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non small cell lung cancer

Limited Utility of Circulating Cell-Free DNA Integrity as a Diagnostic Tool for Differentiating Between Malignant and Benign Thyroid Nodules With Indeterminate Cytology (Bethesda Category III)

Quantitation of cell-free DNA in blood is a potential screening and diagnostic maker of breast cancer: a meta-analysis

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