Cell-free DNA from human plasma and serum differs in content of telomeric sequences and its ability to promote immune response

Zinková, Alžběta; Brynychova, Iva; Svacina, Alexander; Jirkovská, Marie; Korabečná, Marie

doi:10.1038/s41598-017-02905-8

Cited by 39 publications

(31 citation statements)

References 41 publications

(48 reference statements)

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“…Currently, it is still widely discussed, if cfDNA should be extracted from serum or plasma. Some studies discovered that the level of cfDNA was higher in serum compared to plasma [12]; because a part of cfDNA is released during blood cell lysis in the clotting process in tubes before centrifugation, which leads to contamination [13]. Thus, plasma is the preferable biological sample in most studies.…”

Section: Storage and Detection Methods For Cfdnamentioning

confidence: 99%

Circulating tumor DNA as an emerging liquid biopsy biomarker for early diagnosis and therapeutic monitoring in hepatocellular carcinoma

Gassa

et al. 2020

Int. J. Biol. Sci.

111

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As one of the most common malignant tumors worldwide, hepatocellular carcinoma (HCC) is known for its poor prognosis due to diagnosis only in advanced stages. Nearly 50% of the patients with the first diagnosis of HCC die within a year. Currently, the advancements in the integration of omics information have begun to transform the clinical management of cancer patients. Molecular profiling for HCC patients is in general obtained from resected tumor materials or biopsies. However, the resected tumor tissue is limited and can only be obtained through surgery, so that dynamic monitoring of patients cannot be performed. Compared to invasive procedures, circulating tumor DNA (ctDNA) has been proposed as an alternative source to perform molecular profiling of tumor DNA in cancer patients. The detection of abnormal forms of circulating cell-free DNA (cfDNA) that originate from cancer cells (ctDNA) provides a novel tool for cancer detection and disease monitoring. This may also be an opportunity to optimize the early diagnosis of HCC. In this review, we summarized the updated methods, materials, storage of sampling, detection techniques for ctDNA and the comparison of the applications among different biomarkers in HCC patients. In particular, we analyzed ctDNA studies dealing with copy number variations, gene integrity, mutations (RAS, TERT, CTNNB1, TP53 and so on), DNA methylation alterations (DBX2, THY1, TGR5 and so on) for the potential utility of ctDNA in the diagnosis and management of HCC. The biological functions and correlated signaling pathways of ctDNA associated genes (including MAPK/RAS pathway, p53 signaling pathway and Wnt-β catenin pathway) are also discussed and highlighted. Thus, exploration of ctDNA/cfDNA as potential biomarkers may provide a great opportunity in future liquid biopsy applications for HCC.

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Section: Storage and Detection Methods For Cfdnamentioning

confidence: 99%

Circulating tumor DNA as an emerging liquid biopsy biomarker for early diagnosis and therapeutic monitoring in hepatocellular carcinoma

Gassa

et al. 2020

Int. J. Biol. Sci.

111

View full text Add to dashboard Cite

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“…Increasing evidences suggested that it might be passively released by apoptotic and necrotic cells as DNA fragments (24) or actively excreted from distant tumor cells for signal transmission (25). The higher amount of cfDNA was reported from serum compared to plasma (26). Our study found increased concentration of cfDNA in serum within 5 years ahead of clinical diagnosis of GC (data not shown).…”

Section: Figure 2 |mentioning

confidence: 45%

Telomere Length of Circulating Cell-Free DNA and Gastric Cancer in a Chinese Population at High-Risk

Shi

Zhang

et al. 2019

Front. Oncol.

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Background: Telomeres have long been found to be involved in cancer development, while little was known about the dynamic changes of telomere length in carcinogenesis process. Methods: The present study longitudinally investigated telomere alterations of cell-free DNA (cfDNA) in 86 gastric cancer (GC) subjects recruited through a 16-year prospective cohort with 2-4 serums collected before each GC-diagnosis from baseline and three follow-up time-points (a total of 276 samples). As the control, 86 individual-matched cancer-free subjects were enrolled with 276 serums from the matched calendar year. Results: In the 73 pairs of baseline serums from GC and control subjects, shortened telomeres showed increased subsequent GC risk [odds ratio (OR) = 9.17, 95% CI: 2.72-31.25 for 1 unit shortening]. In each baseline gastric lesion category, higher risks of GC progression were also found with shortened cfDNA telomeres; ORs per 1 unit shortening were 6.99 (95% CI: 1.63-30.30) for mild gastric lesions, 6.06 (95% CI: 1.89-19.61) for intestinal metaplasia and 15.63 (95% CI: 1.91-125.00) for dysplasia. With all measurements from baseline and follow-up time-points, shortened telomeres also showed significant association with GC risk (OR = 7.37, 95% CI: 2.06-26.32 for 1 unit shortening). In temporal trend analysis, shortened telomeres were found in GC subjects compared to corresponding controls more than 3 years ahead of GC-diagnosis (most P < 0.05), while no significant difference was found between two groups within 3 years approaching to GC-diagnosis. Conclusion: Our findings suggest that telomere shortening may be associated with gastric carcinogenesis, which supports further etiological study and potential biomarker for risk stratification.

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“…We went on to demonstrate that HOLMES could maintain highconcentration performance in clinical samples and enable the detection of ultralow-abundance molecular biomarkers. In clinical samples, the much more abundant cell-free DNAs [e.g., ∼100 ng/mL in human serum (33)] and proteins [e.g., ∼100 mg/mL in human serum (34)] would present significant noises for the sensitive and specific detection of targets and also suppress the concentration of targets (SI Appendix, section 8). HOLMES uses affinity probes to recognize the targets and modulate their electrophoretic mobility, which enables the selective enrichment of targets and simultaneous depletion of interfering background biomolecules.…”

Section: Nucleic Acid Detection By Holmesmentioning

confidence: 99%

Universal amplification-free molecular diagnostics by billion-fold hierarchical nanofluidic concentration

Ouyang

Han

2019

Proc. Natl. Acad. Sci. U.S.A.

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Rapid and reliable detection of ultralow-abundance nucleic acids and proteins in complex biological media may greatly advance clinical diagnostics and biotechnology development. Currently, nucleic acid tests rely on enzymatic processes for target amplification (e.g., PCR), which have many inherent issues restricting their implementation in diagnostics. On the other hand, there exist no protein amplification techniques, greatly limiting the development of protein-based diagnosis. We report a universal biomolecule enrichment technique termed hierarchical nanofluidic molecular enrichment system (HOLMES) for amplification-free molecular diagnostics using massively paralleled and hierarchically cascaded nanofluidic concentrators. HOLMES achieves billion-fold enrichment of both nucleic acids and proteins within 30 min, which not only overcomes many inherent issues of nucleic acid amplification but also provides unprecedented enrichment performance for protein analysis. HOLMES features the ability to selectively enrich target biomolecules and simultaneously deplete nontargets directly in complex crude samples, thereby enormously enhancing the signal-to-noise ratio of detection. We demonstrate the direct detection of attomolar nucleic acids in urine and serum within 35 min and HIV p24 protein in serum within 60 min. The performance of HOLMES is comparable to that of nucleic acid amplification tests and near million-fold improvement over standard enzyme-linked immunosorbent assay (ELISA) for protein detection, being much simpler and faster in both applications. We additionally measured human cardiac troponin I protein in 9 human plasma samples, and showed excellent agreement with ELISA and detection below the limit of ELISA. HOLMES is in an unparalleled position to unleash the potential of protein-based diagnosis.

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Cell-free DNA from human plasma and serum differs in content of telomeric sequences and its ability to promote immune response

Cited by 39 publications

References 41 publications

Circulating tumor DNA as an emerging liquid biopsy biomarker for early diagnosis and therapeutic monitoring in hepatocellular carcinoma

Circulating tumor DNA as an emerging liquid biopsy biomarker for early diagnosis and therapeutic monitoring in hepatocellular carcinoma

Telomere Length of Circulating Cell-Free DNA and Gastric Cancer in a Chinese Population at High-Risk

Universal amplification-free molecular diagnostics by billion-fold hierarchical nanofluidic concentration

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