scholarly journals Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1448
Author(s):  
Raquel Herranz ◽  
Julia Oto ◽  
Emma Plana ◽  
Álvaro Fernández-Pardo ◽  
Fernando Cana ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Specific Treatment ◽  
Predictive Biomarkers ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Specific Patient ◽  
Free Dna ◽  
Potential Biomarker ◽  
Cancer Types

Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.

scholarly journals Cell-free DNA (cfDNA) and exosome profiling from a year-long human spaceflight reveals circulating biomarkers

2020 ◽  
Author(s):  
Daniela Bezdan ◽  
Kirill Grigorev ◽  
Cem Meydan ◽  
Fanny A. Pelissier Vatter ◽  
Michele Cioffi ◽  
...  
Keyword(s):  
International Space Station ◽  
Space Flight ◽  
Physiological Stress ◽  
Fragment Size ◽  
Space Station ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
International Space ◽  
Free Dna ◽  
Potential Biomarker

AbstractThe health impact of prolonged space flight on the human body is not well understood. Liquid biopsies based on cell-free DNA (cfDNA) or exosome analysis provide a noninvasive approach to monitor the dynamics of genomic, epigenomic and proteomic biomarkers, and the occurrence of DNA damage, physiological stress, and immune responses. To study the molecular consequences of spaceflight we profiled cfDNA isolated from plasma of an astronaut (TW) during a year-long mission on the International Space Station (ISS), sampling before, during, and after spaceflight, and compared the results to cfDNA profiling of the subject’s identical twin (HR) who remained on Earth, as well as healthy donors. We characterized cfDNA concentration and fragment size, and the positioning of nucleosomes on cfDNA, observing a significant increase in the proportion of cell-free mitochondrial DNA inflight, suggesting that cf-mtDNA is a potential biomarker for space flight-associated stress, and that this result was robust to ambient transit from the International Space Station (ISS). Analysis of exosomes isolated from post-flight plasma revealed a 30-fold increase in circulating exosomes and distinct exosomal protein cargo, including brain-derived peptides, in TW compared to HR and all known controls. This study provides the first longitudinal analysis of astronaut cfDNA during spaceflight, as well as the first exosome profiles, and highlights cf-mtDNA levels as a potential biomarker for physiological stress or immune system responses related to microgravity, radiation exposure, and other unique environmental conditions on the ISS.

Circulating cell-free DNA in plasma of colorectal cancer patients - A potential biomarker for tumor burden

2017 ◽  
Vol 26 (4) ◽  
pp. 395-401 ◽  
Author(s):  
Jagdeep Singh Bhangu ◽  
Hossein Taghizadeh ◽  
Tamara Braunschmid ◽  
Thomas Bachleitner-Hofmann ◽  
Christine Mannhalter
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Tumor Burden ◽  
Cell Free Dna ◽  
Free Dna ◽  
Potential Biomarker ◽  
Colorectal Cancer Patients ◽  
Circulating Cell Free Dna

scholarly journals Prediction of cancer progression in a group of 73 gastric cancer patients by circulating cell-free DNA

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Wang-Yang Pu ◽  
Rong Zhang ◽  
Li Xiao ◽  
Yong-You Wu ◽  
Wei Gong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Cell Free Dna ◽  
Free Dna ◽  
Gastric Cancer Patients ◽  
Circulating Cell Free Dna

scholarly journals Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma

2019 ◽  
Vol 37 (18) ◽  
pp. 1547-1557 ◽  
Author(s):  
Emil Christensen ◽  
Karin Birkenkamp-Demtröder ◽  
Himanshu Sethi ◽  
Svetlana Shchegrova ◽  
Raheleh Salari ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Early Detection ◽  
Risk Stratification ◽  
Deep Sequencing ◽  
Therapeutic Efficacy ◽  
Patient Specific ◽  
Cell Free Dna ◽  
Free Dna ◽  
Metastatic Relapse ◽  
Ctdna Analysis

PURPOSE Novel sensitive methods for early detection of relapse and for monitoring therapeutic efficacy may have a huge impact on risk stratification, treatment, and ultimately outcome for patients with bladder cancer. We addressed the prognostic and predictive impact of ultra-deep sequencing of cell-free DNA in patients before and after cystectomy and during chemotherapy. PATIENTS AND METHODS We included 68 patients with localized advanced bladder cancer. Patient-specific somatic mutations, identified by whole-exome sequencing, were used to assess circulating tumor DNA (ctDNA) by ultra-deep sequencing (median, 105,000×) of plasma DNA. Plasma samples (n = 656) were procured at diagnosis, during chemotherapy, before cystectomy, and during surveillance. Expression profiling was performed for tumor subtype and immune signature analyses. RESULTS Presence of ctDNA was highly prognostic at diagnosis before chemotherapy (hazard ratio, 29.1; P = .001). After cystectomy, ctDNA analysis correctly identified all patients with metastatic relapse during disease monitoring (100% sensitivity, 98% specificity). A median lead time over radiographic imaging of 96 days was observed. In addition, for high-risk patients (ctDNA positive before or during treatment), the dynamics of ctDNA during chemotherapy was associated with disease recurrence ( P = .023), whereas pathologic downstaging was not. Analysis of tumor-centric biomarkers showed that mutational processes (signature 5) were associated with pathologic downstaging ( P = .024); however, no significant correlation for tumor subtypes, DNA damage response mutations, and other biomarkers was observed. Our results suggest that ctDNA analysis is better associated with treatment efficacy compared with other available methods. CONCLUSION ctDNA assessment for early risk stratification, therapy monitoring, and early relapse detection in bladder cancer is feasible and provides a basis for clinical studies that evaluate early therapeutic interventions.

scholarly journals Rapid response of stage IV colorectal cancer with APC/TP53/KRAS mutations to FOLFIRI and Bevacizumab combination chemotherapy: a case report of use of liquid biopsy

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Alexander Hendricks ◽  
Philip Rosenstiel ◽  
Sebastian Hinz ◽  
Greta Burmeister ◽  
Christoph Röcken ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Response ◽  
Liquid Biopsy ◽  
Metastatic Cancer ◽  
Stage Iv ◽  
Liquid Biopsies ◽  
Kras Mutations ◽  
Cell Free Dna ◽  
Stage Iv Colorectal Cancer ◽  
Free Dna

Abstract Background Liquid biopsies of blood plasma cell free DNA can be used to monitor treatment response and potentially detect mutations that are present in resistant clones in metastatic cancer patients. Case presentation In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8 months after diagnosis. Retrospective cell free DNA testing showed that the APC/TP53/KRAS major clone responded quickly after 3 cycles of FOLFIRI + Bevacizumab. Retrospective exome sequencing of pre-chemotherapy and post-chemotherapy tissue samples including metastases confirmed that the APC/TP53/KRAS and other major clonal mutations (GPR50, SLC5A, ZIC3, SF3A1 and others) were present in all samples. After the last chemotherapy cycle, CT imaging, CEA and CA19–9 markers validated the cfDNA findings of treatment response. However, 5 weeks later, the tumour had rapidly progressed. Conclusion As FOLFIRI+Bevacizumab has recently also been associated with sustained complete remission in a APC/TP53/KRAS triple-mutated patient, these driver genes should be tested and monitored in a more in-depth manner in future patients. Patients with metastatic disease should be monitored more closely during and after chemotherapy, ideally using cfDNA.

scholarly journals Genome-Wide Analysis of Circulating Cell-Free DNA Copy Number Detects Active Melanoma and Predicts Survival

2018 ◽  
Vol 64 (9) ◽  
pp. 1338-1346 ◽  
Author(s):  
Shobha Silva ◽  
Sarah Danson ◽  
Dawn Teare ◽  
Fiona Taylor ◽  
James Bradford ◽  
...  
Keyword(s):  
Copy Number ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Dna Copy Number ◽  
Cell Free Dna ◽  
Free Dna ◽  
Potential Biomarker ◽  
Melanoma Patients ◽  
Active Disease ◽  
Circulating Cell Free Dna

Abstract BACKGROUND A substantial number of melanoma patients develop local or metastatic recurrence, and early detection of these is vital to maximise benefit from new therapies such as inhibitors of BRAF and MEK, or immune checkpoints. This study explored the use of novel DNA copy-number profiles in circulating cell-free DNA (cfDNA) as a potential biomarker of active disease and survival. PATIENTS AND METHODS Melanoma patients were recruited from oncology and dermatology clinics in Sheffield, UK, and cfDNA was isolated from stored blood plasma. Using low-coverage whole-genome sequencing, we created copy-number profiles from cfDNA from 83 melanoma patients, 44 of whom had active disease. We used scoring algorithms to summarize copy-number aberrations and investigated their utility in multivariable logistic and Cox regression analyses. RESULTS The copy-number aberration score (CNAS) was a good discriminator of active disease (odds ratio, 3.1; 95% CI, 1.5–6.2; P = 0.002), and CNAS above or below the 75th percentile remained a significant discriminator in multivariable analysis for active disease (P = 0.019, with area under ROC curve of 0.90). Additionally, mortality was higher in those with CNASs above the 75th percentile than in those with lower scores (HR, 3.4; 95% CI, 1.5–7.9; P = 0.005), adjusting for stage of disease, disease status (active or resected), BRAF status, and cfDNA concentration. CONCLUSIONS This study demonstrates the potential of a de novo approach utilizing copy-number profiling of cfDNA as a biomarker of active disease and survival in melanoma. Longitudinal analysis of copy-number profiles as an early marker of relapsed disease is warranted.

Circulating cell-free DNA: A potential biomarker to differentiate inflammation and infection during radiochemotherapy

2018 ◽  
Vol 129 (3) ◽  
pp. 575-581 ◽  
Author(s):  
Kerstin Zwirner ◽  
Franz J. Hilke ◽  
German Demidov ◽  
Stephan Ossowski ◽  
Cihan Gani ◽  
...  
Keyword(s):  
Cell Free Dna ◽  
Free Dna ◽  
Potential Biomarker ◽  
Circulating Cell Free Dna

scholarly journals Cell-free DNA promotes malignant transformation in non-tumor cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Aline Gomes de Souza ◽  
Victor Alexandre F. Bastos ◽  
Patricia Tieme Fujimura ◽  
Izabella Cristina C. Ferreira ◽  
Letícia Ferro Leal ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Malignant Transformation ◽  
Cancer Progression ◽  
Biological Fluids ◽  
Cellular Migration ◽  
Cell Phenotype ◽  
Cell Free Dna ◽  
Prostate Cell ◽  
Free Dna

AbstractCell-free DNA is present in different biological fluids and when released by tumor cells may contribute to pro-tumor events such as malignant transformation of cells adjacent to the tumor and metastasis. Thus, this study analyzed the effect of tumor cell-free DNA, isolated from the blood of prostate cancer patients, on non-tumor prostate cell lines (RWPE-1 and PNT-2). To achieve this, we performed cell-free DNA quantification and characterization assays, evaluation of gene and miRNA expression profiling focused on cancer progression and EMT, and metabolomics by mass spectrometry and cellular migration. The results showed that tumor-free cell DNA was able to alter the gene expression of MMP9 and CD44, alter the expression profile of nine miRNAs, and increased the tryptophan consumption and cell migration rates in non-tumor cells. Therefore, tumor cell-free DNA was capable of altering the receptor cell phenotype, triggering events related to malignant transformation in these cells, and can thus be considered a potential target for cancer diagnosis and therapy.

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