Application of Data Science in Circulating Tumor DNA Detection: A Promising Avenue Towards Liquid Biopsy

Li, Ming; Xie, Shuhong; Lu, Chenyu; Zhu, Lingyun; Zhu, Lv‐yun

doi:10.3389/fonc.2021.692322

Cited by 4 publications

(3 citation statements)

References 80 publications

(100 reference statements)

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“…All characteristic signs of genomic DNA from cancer cells have been detected in blood cirDNA; these include point mutations [1], altered microsatellite composition [2], a characteristic methylation profile of tumor suppressor genes [3,4] and repeats [5], and deletions and chromosomal rearrangements [6]. With the development of methods of molecular biology and biochemistry, significant progress has been made in the use of circulating DNA (cirDNA) in practical medicine [7][8][9][10]. In particular, in 2016, the FDA approved the Cobas EGFR Mutation Test v2 (Roche Molecular Systems, Inc., Pleasanton, CA, USA) for the diagnosis of somatic activating mutations in the EGFR gene in the plasma of patients with non-small cell lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Blood Plasma Exosomes Contain Circulating DNA in Their Crown

et al. 2022

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It is known that circulating DNA (cirDNA) is protected from nuclease activity by proteins that form macromolecular complexes with DNA. In addition, it was previously shown that cirDNA can bind to the outer surface of exosomes. NTA analysis and real-time PCR show that exosomes from healthy females (HF) or breast cancer patients (BCP) plasma contain less than 1.4 × 10−8 pg of DNA. Thus, only a minor part of cirDNA is attached to the outer side of the exosome as part of the vesicle crown: the share of exosomal DNA does not exceed 0.025% HF plasma DNA and 0.004% BCP plasma DNA. Treatment of plasma exosomes with DNase I with subsequent dot immunoassay reveals that H2a, H2b, and H3 histones are not part of the exosomal membrane, but are part of the cirDNA–protein macromolecular complex associated with the surface of the exosome either through interaction with DNA-binding proteins or with histone-binding proteins. Using bioinformatics approaches after identification by MALDI-TOF mass spectrometry, 16 exosomal DNA-binding proteins were identified. It was shown that four proteins—AIFM1, IGHM, CHD5, and KCNIP3—are candidates for DNA binding on the outer membrane of exosomes; the crown of exosomes may include five DNA-binding proteins: H2a, H2b, H3, IGHM, and ALB. Of note, AIFM1, IGHM, and CHD5 proteins are found only in HF plasma exosomes; KCNIP3 protein is identified only in BCP plasma exosomes; and H2a, H2b, H3, and ALB are revealed in all samples of plasma exosomes. Two histone-binding proteins, CHD5 and KDM6B, have been found in exosomes from HF plasma. The data obtained indicate that cirDNA preferentially binds to the outer membrane of exosomes by association with DNA-binding proteins.

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Section: Introductionmentioning

confidence: 99%

Blood Plasma Exosomes Contain Circulating DNA in Their Crown

et al. 2022

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“…Although the advantages of LBs in the evaluation of OSCC prognosis, risk stratification, or its use as a tool for precision medicine development, has been discussed here, a very challenging aspect is its reproducibility across multiple centers, to establish a standard guideline for LB-based cancer diagnostics. The development of LB databases such as liqDB [ 87 ], ctcRbase [ 88 , 89 ], and BloodPAC Data Commons (BPDC) [ 90 ], has helped to overcome such technical issues and has encouraged data science research to address the practical and conceptual reproducibility problems associated with the use of LB [ 91 ]. Hence, the development of an OSCC LB database in Africa and other resource-limited settings, could potentially ameliorate the diagnostic and treatment burden of OSCC in these regions.…”

Section: Future Perspectives Of Liquid Biopsy In Africamentioning

confidence: 99%

The Practicality of the Use of Liquid Biopsy in Early Diagnosis and Treatment Monitoring of Oral Cancer in Resource-Limited Settings

Adeola

Bello

Aruleba

et al. 2022

Cancers

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An important driving force for precision and individualized medicine is the provision of tailor-made care for patients on an individual basis, in accordance with best evidence practice. Liquid biopsy(LB) has emerged as a critical tool for the early diagnosis of cancer and for treatment monitoring, but its clinical utility for oral squamous cell carcinoma (OSCC) requires more research and validation. Hence, in this review, we have discussed the current applications of LB and the practicality of its routine use in Africa; the potential advantages of LB over the conventional “gold-standard” of tissue biopsy; and finally, practical considerations were discussed in three parts: pre-analytic, analytic processing, and the statistical quality and postprocessing phases. Although it is imperative to establish clinically validated and standardized working guidelines for various aspects of LB sample collection, processing, and analysis for optimal and reliable use, manpower and technological infrastructures may also be an important factor to consider for the routine clinical application of LB for OSCC. LB is poised as a non-invasive precision tool for personalized oral cancer medicine, particularly for OSCC in Africa, when fully embraced. The promising application of different LB approaches using various downstream analyses such as released circulating tumor cells (CTCs), cell free DNA (cfDNA), microRNA (miRNA), messenger RNA (mRNA), and salivary exosomes were discussed. A better understanding of the diagnostic and therapeutic biomarkers of OSCC, using LB applications, would significantly reduce the cost, provide an opportunity for prompt detection and early treatment, and a method to adequately monitor the effectiveness of the therapy for OSCC, which typically presents with ominous prognosis.

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“…Circulating DNA (cirDNA) has already proven to be a valuable tool in translational medicine [1][2][3]. However, one overlooked area of cirDNA research is its association with various proteins, despite considerable evidence that this interaction may influence the fate of DNA in the bloodstream and its molecular functions [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Blood Plasma Circulating DNA-Protein Complexes: Involvement in Carcinogenesis and Prospects for Liquid Biopsy of Breast Cancer

Shefer,

Tutanov,

Belenikin

et al. 2023

JPM

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Circulating DNA (cirDNA) is a promising tool in translational medicine. However, studies of cirDNA have neglected its association with proteins, despite ample evidence that this interaction may affect the fate of DNA in the bloodstream and its molecular functions. The goal of the current study is to shed light on the differences between the proteomic cargos of histone-containing nucleoprotein complexes (NPCs) from healthy female (HFs) and breast cancer patients (BCPs), and to reveal the proteins involved in carcinogenesis. NPCs were isolated from the blood samples of HFs and BCPs using affinity chromatography. A total of 177 and 169 proteins were identified in NPCs from HFs and BCPs using MALDI-TOF mass spectrometry. A bioinformatics analysis revealed that catalytically active proteins, as well as proteins that bind nucleic acids and regulate the activity of receptors, are the most represented among the unique proteins of blood NPCs from HFs and BCPs. In addition, the proportion of proteins participating in ion channels and proteins binding proteins increases in the NPCs from BCP blood. However, the involvement in transport and signal transduction was greater in BCP NPCs compared to those from HFs. Gene ontology term (GO) analysis revealed that the NPC protein cargo from HF blood was enriched with proteins involved in the negative regulation of cell proliferation, and in BCP blood, proteins involved in EMT, invasion, and cell migration were observed. The combination of SPG7, ADRB1, SMCO4, PHF1, and PSMG1 NPC proteins differentiates BCPs from HFs with a sensitivity of 100% and a specificity of 80%. The obtained results indirectly indicate that, in tandem with proteins, blood cirDNA is an important part of intercellular communication, playing a regulatory and integrating role in the physiology of the body.

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Application of Data Science in Circulating Tumor DNA Detection: A Promising Avenue Towards Liquid Biopsy

Cited by 4 publications

References 80 publications

Blood Plasma Exosomes Contain Circulating DNA in Their Crown

Blood Plasma Exosomes Contain Circulating DNA in Their Crown

The Practicality of the Use of Liquid Biopsy in Early Diagnosis and Treatment Monitoring of Oral Cancer in Resource-Limited Settings

Blood Plasma Circulating DNA-Protein Complexes: Involvement in Carcinogenesis and Prospects for Liquid Biopsy of Breast Cancer

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