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Sobhani N, Tierno D, Pavan N, Generali D, Grassi G, Zanconati F, Scaggiante B. Circulating Cell-Free DNA Integrity for Breast and Prostate Cancer: What Is the Landscape for Clinical Management of the Most Common Cancers in Women and Men? Int J Mol Sci 2025; 26:900. [PMID: 39940669 PMCID: PMC11817310 DOI: 10.3390/ijms26030900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 01/16/2025] [Accepted: 01/20/2025] [Indexed: 02/16/2025] Open
Abstract
Breast cancer (BC) and prostate cancer (PCa) are major health problems for women and men worldwide. Although therapeutic approaches have increased, the complexity associated with their heterogeneity and progression requires better ways to monitor them over time. Cell-free DNA integrity (cfDI) represents a viable alternative to needle biopsy and has the potential to be representative of cancer at all stages. In addition to the advantages of liquid biopsy in terms of cost and reduced invasiveness, cfDI can be used to detect repetitive DNA elements (e.g., ALU and LINE1), which could circumvent the problem of mutational heterogeneity in BC and PCa. In this review, we summarise the latest findings on cfDI studies in BC and PCa. The results show that cfDI has the potential to improve early detection, metastasis, and recurrence of BC, while limited studies prevent its clinical value in PCa from being fully defined. However, it is expected that further studies in the near future will help to introduce the use of cfDI as another biomarker for the clinical monitoring of BC and PCa patients.
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Affiliation(s)
- Navid Sobhani
- Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA;
| | - Domenico Tierno
- Department of Medicine, Surgery and Health Sciences, University Hospital of Cattinara, University of Trieste, 34149 Trieste, Italy; (D.T.); (D.G.); (G.G.); (F.Z.)
| | - Nicola Pavan
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy;
| | - Daniele Generali
- Department of Medicine, Surgery and Health Sciences, University Hospital of Cattinara, University of Trieste, 34149 Trieste, Italy; (D.T.); (D.G.); (G.G.); (F.Z.)
- Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, 26100 Cremona, Italy
| | - Gabriele Grassi
- Department of Medicine, Surgery and Health Sciences, University Hospital of Cattinara, University of Trieste, 34149 Trieste, Italy; (D.T.); (D.G.); (G.G.); (F.Z.)
| | - Fabrizio Zanconati
- Department of Medicine, Surgery and Health Sciences, University Hospital of Cattinara, University of Trieste, 34149 Trieste, Italy; (D.T.); (D.G.); (G.G.); (F.Z.)
| | - Bruna Scaggiante
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
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Giro C, Yamada AMTD, Cruz FJSM, do R Barros LA, da C A Alves B, Fonseca FLA, Del Giglio A. Measuring cfDNA integrity as a biomarker for predicting neoadjuvant chemotherapy response in breast cancer patients: a pilot study. Breast Cancer Res Treat 2024; 206:329-335. [PMID: 38743176 DOI: 10.1007/s10549-024-07366-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 04/24/2024] [Indexed: 05/16/2024]
Abstract
PURPOSE Circulating cell-free DNA (cfDNA) is a promising biomarker for predicting treatment response and disease outcomes in Breast Cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). To determine if cfDNA originates from tumors, matching tumor and cfDNA gene mutations are necessary, often requiring tumor DNA sequencing. We assessed plasma cfDNA integrity by measuring concentrations and ratios of larger-to-smaller Alu DNA fractions as a potential biomarker, eliminating the need for prior tumor sequencing. METHODS We included patients with localized and/or locally advanced BC receiving standard NAC alone or in combination with immunotherapy and/or anti-HER2 targeted therapy. Blood samples were collected before treatment, every 2 weeks during treatment, and before surgery. RESULTS Of the 38 evaluated patients, only 28 completed the protocol and underwent surgery after NAC. Seven patients (25%) achieved a pathologic complete response (pCR). We found that cfDNA integrity (cfDNAI) levels at 15 days after starting NAC were significantly higher in patients who achieved pCR (p = 0.045) and correlated significantly with Disease-Free Survival (DFS) in univariate analysis (p = 0.0371). CONCLUSIONS Evaluation of cfDNAI 2 weeks after NAC initiation appears to be an early biomarker for tumor pCR and DFS. Measuring Alu fragments of different lengths may replace techniques requiring prior tumor sequencing to measure ctDNA, reducing costs and complexity of cfDNA serial measurements in BC patients undergoing NAC.
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Affiliation(s)
- Camila Giro
- Instituto Brasileiro de Controle do Câncer (IBCC), São Paulo, SP, Brazil
- Departamento de Oncologia e Hematologia do Centro Universitário FMABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil
| | | | - Felipe José S M Cruz
- Instituto Brasileiro de Controle do Câncer (IBCC), São Paulo, SP, Brazil
- Departamento de Oncologia e Hematologia do Centro Universitário FMABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil
| | | | - Beatriz da C A Alves
- Laboratório de Análises Clínicas do Centro Universitário FMABC, Santo André, SP, Brazil
| | - Fernando L A Fonseca
- Laboratório de Análises Clínicas do Centro Universitário FMABC, Santo André, SP, Brazil
- Instituto de Ciências Farmacêuticas, Universidade Federal de São Paulo (UNIFESP), Diadema, SP, Brazil
| | - Auro Del Giglio
- Departamento de Oncologia e Hematologia do Centro Universitário FMABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil.
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Xu J, Gao H, Guan X, Meng J, Ding S, Long Q, Yi W. Circulating tumor DNA: from discovery to clinical application in breast cancer. Front Immunol 2024; 15:1355887. [PMID: 38745646 PMCID: PMC11091288 DOI: 10.3389/fimmu.2024.1355887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 04/16/2024] [Indexed: 05/16/2024] Open
Abstract
Breast cancer (BC) stands out as the cancer with the highest incidence of morbidity and mortality among women worldwide, and its incidence rate is currently trending upwards. Improving the efficiency of breast cancer diagnosis and treatment is crucial, as it can effectively reduce the disease burden. Circulating tumor DNA (ctDNA) originates from the release of tumor cells and plays a pivotal role in the occurrence, development, and metastasis of breast cancer. In recent years, the widespread application of high-throughput analytical technology has made ctDNA a promising biomarker for early cancer detection, monitoring minimal residual disease, early recurrence monitoring, and predicting treatment outcomes. ctDNA-based approaches can effectively compensate for the shortcomings of traditional screening and monitoring methods, which fail to provide real-time information and prospective guidance for breast cancer diagnosis and treatment. This review summarizes the applications of ctDNA in various aspects of breast cancer, including screening, diagnosis, prognosis, treatment, and follow-up. It highlights the current research status in this field and emphasizes the potential for future large-scale clinical applications of ctDNA-based approaches.
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Affiliation(s)
- Jiachi Xu
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center For Breast Disease In Hunan Province, Changsha, China
| | - Hongyu Gao
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center For Breast Disease In Hunan Province, Changsha, China
| | - Xinyu Guan
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center For Breast Disease In Hunan Province, Changsha, China
| | - Jiahao Meng
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center For Breast Disease In Hunan Province, Changsha, China
| | - Shirong Ding
- Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Qian Long
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center For Breast Disease In Hunan Province, Changsha, China
| | - Wenjun Yi
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center For Breast Disease In Hunan Province, Changsha, China
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Douville C, Lahouel K, Kuo A, Grant H, Avigdor BE, Curtis SD, Summers M, Cohen JD, Wang Y, Mattox A, Dudley J, Dobbyn L, Popoli M, Ptak J, Nehme N, Silliman N, Blair C, Romans K, Thoburn C, Gizzi J, Schoen RE, Tie J, Gibbs P, Ho-Pham LT, Tran BNH, Tran TS, Nguyen TV, Goggins M, Wolfgang CL, Wang TL, Shih IM, Lennon AM, Hruban RH, Bettegowda C, Kinzler KW, Papadopoulos N, Vogelstein B, Tomasetti C. Machine learning to detect the SINEs of cancer. Sci Transl Med 2024; 16:eadi3883. [PMID: 38266106 PMCID: PMC11210392 DOI: 10.1126/scitranslmed.adi3883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 12/22/2023] [Indexed: 01/26/2024]
Abstract
We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the validation cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and eight common protein biomarkers detected 51% of the cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature-the global reduction of AluS subfamily elements in the circulating DNA of patients with solid cancer. We confirmed this reduction through the analysis of another independent dataset obtained with a different approach (whole-genome sequencing). The evaluation of Alu elements may therefore have the potential to enhance the performance of several methods designed for the earlier detection of cancer.
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Affiliation(s)
- Christopher Douville
- Division of Quantitative Sciences, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Kamel Lahouel
- Center for Cancer Prevention and Early Detection, City of Hope, Duarte, CA 91010, USA
- Center for Cancer Prevention and Early Detection, City of Hope, Division of Mathematics for Cancer Evolution and Early Detection, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
- Division of Integrated Cancer Genomics, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
- Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, MD 21205, USA
| | - Albert Kuo
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, MD 21205, USA
| | - Haley Grant
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, MD 21205, USA
| | - Bracha Erlanger Avigdor
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Samuel D. Curtis
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Mahmoud Summers
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Joshua D. Cohen
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Yuxuan Wang
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Austin Mattox
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jonathan Dudley
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Pathology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Lisa Dobbyn
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Maria Popoli
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Janine Ptak
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Nadine Nehme
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Natalie Silliman
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Cherie Blair
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Katharine Romans
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Christopher Thoburn
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Jennifer Gizzi
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Robert E. Schoen
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
- Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
| | - Jeanne Tie
- Division of Personalized Oncology, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Melbourne, VIC 3000, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3011, Australia
| | - Peter Gibbs
- Division of Personalized Oncology, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Melbourne, VIC 3000, Australia
- Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3010, Australia
| | - Lan T. Ho-Pham
- BioMedical Research Center, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 72510, Vietnam
- Clinical Genetics Research Group, Saigon Precision Medicine Research Center, Ho Chi Minh City 72512, Vietnam
| | - Bich N. H. Tran
- Saigon Precision Medicine Research Center, Ho Chi Minh City 72512, Vietnam
| | - Thach S. Tran
- Saigon Precision Medicine Research Center, Ho Chi Minh City 72512, Vietnam
- School of Biomedical Engineering, University of Technology Sydney, NSW 2007, Australia
| | - Tuan V. Nguyen
- Saigon Precision Medicine Research Center, Ho Chi Minh City 72512, Vietnam
- School of Biomedical Engineering, University of Technology Sydney, NSW 2007, Australia
- Tâm Anh Research Institute, Ho Chi Minh City, Vietnam
- Centre for Health Technologies, University of Technology, NSW 2007, Australia
- School of Population Health, University of New South Wales, NSW 2003, Australia
| | - Michael Goggins
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Department of Pathology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Department of Medicine, Johns Hopkins Medical Institutes, 733 N. Broadway, Baltimore, MD 21205, USA
| | | | - Tian-Li Wang
- Department of Pathology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
| | - Ie-Ming Shih
- Department of Pathology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
| | - Anne Marie Lennon
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Medicine, Johns Hopkins Medical Institutes, 733 N. Broadway, Baltimore, MD 21205, USA
- Department of Surgery, Johns Hopkins Medical Institutes, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Ralph H. Hruban
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Department of Pathology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Chetan Bettegowda
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Neurosurgery, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Kenneth W. Kinzler
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Nickolas Papadopoulos
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Bert Vogelstein
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Cristian Tomasetti
- Center for Cancer Prevention and Early Detection, City of Hope, Duarte, CA 91010, USA
- Center for Cancer Prevention and Early Detection, City of Hope, Division of Mathematics for Cancer Evolution and Early Detection, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
- Division of Integrated Cancer Genomics, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
- Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, MD 21205, USA
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5
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Guil-Luna S, Sánchez-Céspedes R, Rivas Crespo A, Dolores Fernández M, Fernández Sarmiento JA, Rodríguez-Ariza A, Millán Y. Analysis of cell-free DNA concentration, fragmentation patterns and TP53 gene expression in mammary tumor-bearing dogs: A pilot study. Front Vet Sci 2023; 10:1157878. [PMID: 37065257 PMCID: PMC10090457 DOI: 10.3389/fvets.2023.1157878] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 03/08/2023] [Indexed: 03/31/2023] Open
Abstract
IntroductionLiquid biopsy based on the analysis of circulating cell-free DNA (cfDNA), as well as on detection of point mutations by digital droplet PCR (ddPCR), has revolutionized the research in oncology. In recent years, this technique has been pioneering in veterinary medicine since it is a minimally invasive approach with very promising results for characterization of tumors.MethodsThe aim of this study was, firstly, to analyze the concentration and the fragmentation pattern of cfDNA of dogs with mammary tumors (n = 36) and healthy dogs (n = 5) and its correlation with clinicopathological data. Secondly, analysis of TP53 gene expression and the point mutation in the codon 245 were performed in cfDNA and in tumor tissues to assess their potential as plasma biomarkers.Results and discussionOur results highlighted that those dogs with worse clinicopathological characteristics (simple or undifferentiated carcinomas, higher histological grade and presence of peritumoral inflammation) shown higher cfDNA concentration and higher concentrations of short-fragments (<190 bp) than healthy dogs. In addition, although no detection of the point mutation in codon 245 of TP53 gene could be detected neither in plasma nor tumor tissue, an increased TP53 expression was detected in animals with tumors bearing malignant characteristics. Finally, a high concordance with TP53 gene expression in plasma and tumor tissue and cfDNA concentration was also found. The results derived from this work confirm the valuable potential of cfDNA and its fragments, as well as the analysis of TP53 expression in plasma as useful liquid biomarkers for clinical application in veterinary oncology.
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Affiliation(s)
- Silvia Guil-Luna
- Grupo Nuevas Terapias en cáncer, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
- Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria de Córdoba, Universidad de Córdoba, Córdoba, Spain
- *Correspondence: Silvia Guil-Luna
| | - Raquel Sánchez-Céspedes
- Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria de Córdoba, Universidad de Córdoba, Córdoba, Spain
| | - Aurora Rivas Crespo
- Grupo Nuevas Terapias en cáncer, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain
| | - María Dolores Fernández
- Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria de Córdoba, Universidad de Córdoba, Córdoba, Spain
| | | | - Antonio Rodríguez-Ariza
- Grupo Nuevas Terapias en cáncer, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
| | - Yolanda Millán
- Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria de Córdoba, Universidad de Córdoba, Córdoba, Spain
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6
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Nair MG, Ramesh RS, Naidu CM, Mavatkar AD, V. P. S, Ramamurthy V, Somashekaraiah VM, C. E. A, Raghunathan K, Panigrahi A, Das M, Dhar SK, Prabhu JS. Estimation of ALU Repetitive Elements in Plasma as a Cost-Effective Liquid Biopsy Tool for Disease Prognosis in Breast Cancer. Cancers (Basel) 2023; 15:cancers15041054. [PMID: 36831397 PMCID: PMC9953974 DOI: 10.3390/cancers15041054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/20/2023] [Accepted: 01/23/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND Liquid biopsy is widely recognized as an efficient diagnostic method in oncology for disease detection and monitoring. Though the examination of circulating tumor cells (CTC) is mostly implemented for the assessment of genomic aberrations, the need of complex methodologies for their detection has impeded its acceptance in low-resource settings. We evaluated cell-free DNA (cfDNA) as a liquid biopsy tool and investigated its utility in breast cancer patients. METHODS Total cell-free DNA was extracted from the plasma of breast cancer patients (n = 167) with a median follow-up of more than 5 years, at various stages of the disease. Quantitative PCR was performed to estimate the copy numbers of two fractions of ALU repetitive elements (ALU 115 and ALU 247), and DNA integrity (DI) was calculated as the ratio of ALU 247/115. Mutations in TP53 and PIK3CA in the cfDNA were estimated by next-gen sequencing (NGS) in a subset of samples. Associations of the levels of both the ALU fragments with various clinico-pathological factors and disease-free survival at various stages were examined. Nomogram models were constructed with clinical variables and ALU 247 levels to predict disease-free survival and the best performing model was evaluated by decision curve analysis. RESULTS DI and ALU 247 levels were significantly lower (p < 0.0001) in the post-operative plasma when compared to their pre-surgery levels. DI and ALU 247 were found to be significantly higher in patients with metastasis (p < 0.05). Patients with higher levels of ALU 247 in their post-operative plasma had significant poor disease-free survival (p = 0.005). Higher levels of ALU 247 in the circulation also correlated with low tumor-infiltrating lymphocytes (TIL) within their primary tumors in the ER-negative breast cancer subtype (p = 0.01). Cox proportional hazard analysis confirmed ALU 247 as an independent variable of disease-free survival both in univariate and multivariate analysis [HR 1.3 (95% CI 1.047 to 1.613, p = 0.017)]. The nomogram model showed that the addition of ALU 247 with other variables significantly improved (C-index 0.823) the predictive ability of the model. CONCLUSION Our results confirm the utility of cfDNA as an evolving liquid biopsy tool for molecular analysis. Evaluation of larger fragments of cfDNA estimated through ALU 247 can provide vital information concurrent with the pathological process of disease evolution in breast cancer and warrants expansion to other cancer types.
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Affiliation(s)
- Madhumathy G. Nair
- Division of Molecular Medicine, St. John’s Research Institute, St. John’s Medical College, Bangalore 560034, India
- Correspondence: (M.G.N.); (J.S.P.)
| | - Rakesh S. Ramesh
- Department of Surgical Oncology, St. John’s Medical College and Hospital, Bangalore 560034, India
| | - Chandrakala M. Naidu
- Division of Molecular Medicine, St. John’s Research Institute, St. John’s Medical College, Bangalore 560034, India
| | - Apoorva D. Mavatkar
- Division of Molecular Medicine, St. John’s Research Institute, St. John’s Medical College, Bangalore 560034, India
| | - Snijesh V. P.
- Division of Molecular Medicine, St. John’s Research Institute, St. John’s Medical College, Bangalore 560034, India
| | - Vishakha Ramamurthy
- Division of Molecular Medicine, St. John’s Research Institute, St. John’s Medical College, Bangalore 560034, India
| | - Vidya M. Somashekaraiah
- Division of Molecular Medicine, St. John’s Research Institute, St. John’s Medical College, Bangalore 560034, India
| | - Anupama C. E.
- Division of Molecular Medicine, St. John’s Research Institute, St. John’s Medical College, Bangalore 560034, India
| | | | - Anuradha Panigrahi
- Molecular Immunology Program, MSMF, Narayana Health City, Bangalore 560099, India
| | - Manjula Das
- Molecular Immunology Program, MSMF, Narayana Health City, Bangalore 560099, India
| | - Sujan K. Dhar
- Molecular Immunology Program, MSMF, Narayana Health City, Bangalore 560099, India
| | - Jyothi S. Prabhu
- Division of Molecular Medicine, St. John’s Research Institute, St. John’s Medical College, Bangalore 560034, India
- Correspondence: (M.G.N.); (J.S.P.)
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7
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Gianni C, Palleschi M, Merloni F, Bleve S, Casadei C, Sirico M, Di Menna G, Sarti S, Cecconetto L, Mariotti M, De Giorgi U. Potential Impact of Preoperative Circulating Biomarkers on Individual Escalating/de-Escalating Strategies in Early Breast Cancer. Cancers (Basel) 2022; 15:96. [PMID: 36612091 PMCID: PMC9817806 DOI: 10.3390/cancers15010096] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/18/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
The research on non-invasive circulating biomarkers to guide clinical decision is in wide expansion, including the earliest disease settings. Several new intensification/de-intensification strategies are approaching clinical practice, personalizing the treatment for each patient. Moreover, liquid biopsy is revealing its potential with multiple techniques and studies available on circulating biomarkers in the preoperative phase. Inflammatory circulating cells, circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and other biological biomarkers are improving the armamentarium for treatment selection. Defining the escalation and de-escalation of treatments is a mainstay of personalized medicine in early breast cancer. In this review, we delineate the studies investigating the possible application of these non-invasive tools to give a more enlightened approach to escalating/de-escalating strategies in early breast cancer.
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Affiliation(s)
- Caterina Gianni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
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8
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Gianni C, Palleschi M, Merloni F, Di Menna G, Sirico M, Sarti S, Virga A, Ulivi P, Cecconetto L, Mariotti M, De Giorgi U. Cell-Free DNA Fragmentomics: A Promising Biomarker for Diagnosis, Prognosis and Prediction of Response in Breast Cancer. Int J Mol Sci 2022; 23:14197. [PMID: 36430675 PMCID: PMC9695769 DOI: 10.3390/ijms232214197] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/04/2022] [Accepted: 11/16/2022] [Indexed: 11/18/2022] Open
Abstract
Identifying novel circulating biomarkers predictive of response and informative about the mechanisms of resistance, is the new challenge for breast cancer (BC) management. The integration of omics information will gradually revolutionize the clinical approach. Liquid biopsy is being incorporated into the diagnostic and decision-making process for the treatment of BC, in particular with the analysis of circulating tumor DNA, although with some relevant limitations, including costs. Circulating cell-free DNA (cfDNA) fragmentomics and its integrity index may become a cheaper, noninvasive biomarker that could provide significant additional information for monitoring response to systemic treatments in BC. The purpose of our review is to focus on the available research on cfDNA integrity and its features as a biomarker of diagnosis, prognosis and response to treatments in BC, highlighting new perspectives and critical issues for future applications.
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Affiliation(s)
- Caterina Gianni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Michela Palleschi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Filippo Merloni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Giandomenico Di Menna
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Marianna Sirico
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Samanta Sarti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Alessandra Virga
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Paola Ulivi
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Lorenzo Cecconetto
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Marita Mariotti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Ugo De Giorgi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
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9
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The Utility of Repetitive Cell-Free DNA in Cancer Liquid Biopsies. Diagnostics (Basel) 2022; 12:diagnostics12061363. [PMID: 35741173 PMCID: PMC9221655 DOI: 10.3390/diagnostics12061363] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 05/27/2022] [Accepted: 05/30/2022] [Indexed: 02/05/2023] Open
Abstract
Liquid biopsy is a broad term that refers to the testing of body fluids for biomarkers that correlate with a pathological condition. While a variety of body-fluid components (e.g., circulating tumor cells, extracellular vesicles, RNA, proteins, and metabolites) are studied as potential liquid biopsy biomarkers, cell-free DNA (cfDNA) has attracted the most attention in recent years. The total cfDNA population in a typical biospecimen represents an immensely rich source of biological and pathological information and has demonstrated significant potential as a versatile biomarker in oncology, non-invasive prenatal testing, and transplant monitoring. As a significant portion of cfDNA is composed of repeat DNA sequences and some families (e.g., pericentric satellites) were recently shown to be overrepresented in cfDNA populations vs their genomic abundance, it holds great potential for developing liquid biopsy-based biomarkers for the early detection and management of patients with cancer. By outlining research that employed cell-free repeat DNA sequences, in particular the ALU and LINE-1 elements, we highlight the clinical potential of the repeat-element content of cfDNA as an underappreciated marker in the cancer liquid biopsy repertoire.
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10
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Shaban S, Al‑Rahim A, Suleiman A. ALU repeat as potential molecular marker in the detection and prognosis of different cancer types: A systematic review. Mol Clin Oncol 2022; 16:86. [PMID: 35251637 PMCID: PMC8892463 DOI: 10.3892/mco.2022.2519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/13/2022] [Indexed: 11/25/2022] Open
Abstract
Cancer is a major health issue worldwide. cfDNA integrity has been reported as a potential diagnostic molecular marker for different types of cancer, identifying the importance of liquid biopsy. The aim of this review was to evaluate the prognostic and diagnostic performance of Arthrobacter luteus (ALU) repeat in tumor. Following a thorough review of the literature published from January, 2000 to September 2021, 36 studies were included. All of the study descriptions were analyzed. According to several studies, there were increased concentrations of ALU repetitive elements in cancer patients, while these concentrations were decreased in control, benign, different cancer stage, and other diseases. The total ALU (115 and 247) sequence levels are potential biomarkers for the purpose of investigations and cancer prognosis.
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Affiliation(s)
- Semaa Shaban
- Department of Biology, College of Sciences, Tikrit University, Tikrit, Saladin 34001, Iraq
| | - Aya Al‑Rahim
- Department of Molecular and Medical Biotechnology, College of Biotechnology, Al‑Nahrain University, Baghdad 64074, Iraq
| | - Ahmed Suleiman
- Department of Biotechnology, Science College, University of Anbar, Ramadi, Anbar 46006, Iraq
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11
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Liu APY, Smith KS, Kumar R, Paul L, Bihannic L, Lin T, Maass KK, Pajtler KW, Chintagumpala M, Su JM, Bouffet E, Fisher MJ, Gururangan S, Cohn R, Hassall T, Hansford JR, Klimo P, Boop FA, Stewart CF, Harreld JH, Merchant TE, Tatevossian RG, Neale G, Lear M, Klco JM, Orr BA, Ellison DW, Gilbertson RJ, Onar-Thomas A, Gajjar A, Robinson GW, Northcott PA. Serial assessment of measurable residual disease in medulloblastoma liquid biopsies. Cancer Cell 2021; 39:1519-1530.e4. [PMID: 34678152 PMCID: PMC9620970 DOI: 10.1016/j.ccell.2021.09.012] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 07/18/2021] [Accepted: 09/22/2021] [Indexed: 12/20/2022]
Abstract
Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging, and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.
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Affiliation(s)
- Anthony P Y Liu
- Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Kyle S Smith
- Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Rahul Kumar
- Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; St. Jude Graduate School of Biomedical Sciences, Memphis, TN 38105, USA
| | - Leena Paul
- Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Laure Bihannic
- Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Tong Lin
- Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Kendra K Maass
- Division of Pediatric Neuro-oncology, German Cancer Research Center, 69120 Heidelberg, Germany
| | - Kristian W Pajtler
- Division of Pediatric Neuro-oncology, German Cancer Research Center, 69120 Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, 69120 Heidelberg, Germany
| | - Murali Chintagumpala
- Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
| | - Jack M Su
- Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
| | - Eric Bouffet
- Division of Hematology-Oncology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
| | - Michael J Fisher
- Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Sridharan Gururangan
- Preston A. Wells Jr. Center for Brain Tumor Therapy, UF Health Shands Hospital, Gainesville, FL 32608, USA
| | - Richard Cohn
- Kids Cancer Centre, Sydney Children's Hospital, Randwick, and UNSW, Sydney, NSW 2031, Australia
| | - Tim Hassall
- Queensland Children's Hospital, Brisbane, QLD 4101, Australia
| | - Jordan R Hansford
- Children's Cancer Centre, The Royal Children's Hospital, Murdoch Children's Research Institute, Department of Pediatrics, University of Melbourne, Melbourne, VIC 3052, Australia
| | - Paul Klimo
- Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN 38105, USA; Le Bonheur Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, TN 38105, USA
| | - Frederick A Boop
- Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN 38105, USA; Le Bonheur Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, TN 38105, USA
| | - Clinton F Stewart
- Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Julie H Harreld
- Department of Radiology, Dartmouth Geisel School of Medicine, Hanover, NH 03755, USA
| | - Thomas E Merchant
- Department of Radiation Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Ruth G Tatevossian
- Diagnostic Biomarkers Shared Resource, Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Geoffrey Neale
- Hartwell Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Matthew Lear
- Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Jeffery M Klco
- Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Brent A Orr
- Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - David W Ellison
- Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Richard J Gilbertson
- Cancer Research UK Cambridge Centre, CRUK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK
| | - Arzu Onar-Thomas
- Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Amar Gajjar
- Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Giles W Robinson
- Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Paul A Northcott
- Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
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12
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Duque G, Manterola C, Otzen T, Arias C, Galindo B, Mora M, Guerrero E, García N. Clinical utility of liquid biopsy in breast cancer: A systematic review. Clin Genet 2021; 101:285-295. [PMID: 34687555 DOI: 10.1111/cge.14077] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 10/14/2021] [Accepted: 10/15/2021] [Indexed: 12/18/2022]
Abstract
Advancements in genetic sequencing techniques along with the identification of specific mutations and structural changes in multiple cancer genes, make it possible to identify circulating tumor cells and cell free nucleic acids as blood-based biomarkers, serving as a liquid biopsy (LB) with great utility for the diagnosis, treatment and follow-up of patients with neoplasms. This systematic review focuses on the clinical utility of LB in patients with breast cancer (BC). Articles published between 1990 and 2021 were included. Databases searched: Trip Database, WoS, EMBASE, PubMed, SCOPUS, and Clinical Keys. Variables studied: Publication year, country, number of cases, primary study design, LB detection methods, genes found, overall survival, disease-free survival, stage, response to treatment, clinical utility, BC molecular type, systemic treatment and methodological quality of primary studies. Of 2619 articles, 74 were retained representing 12 658 patients, mainly cohort studies (66.2%), the majority were from China (15%) and Japan (12.2%). All primary studies described clinical stage and type of systemic treatment used. Most used biomarker detection method: DNA (52.7%) and type of analysis: quantification of total cfDNA (35.1%). PIK3CA mutation was most frequent (62.9%). Evidence suggests clinically useful applications of BC. Though heterogeneous, publications suggest that LB will constitute part of the standard diagnostic-therapeutic process of BC.
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Affiliation(s)
- Galo Duque
- PhD Program in Medical Sciences, Universidad de La Frontera, Temuco, Chile.,Faculty of Medicine, Universidad del Azuay, Cuenca, Ecuador
| | - Carlos Manterola
- PhD Program in Medical Sciences, Universidad de La Frontera, Temuco, Chile.,Center of Excellence in Morphological and Surgical Studies (CEMyQ), Universidad de La Frontera, Temuco, Chile
| | - Tamara Otzen
- PhD Program in Medical Sciences, Universidad de La Frontera, Temuco, Chile.,Center of Excellence in Morphological and Surgical Studies (CEMyQ), Universidad de La Frontera, Temuco, Chile
| | - Cristina Arias
- Faculty of Medicine, Universidad del Azuay, Cuenca, Ecuador
| | - Bryan Galindo
- Faculty of Medicine, Universidad del Azuay, Cuenca, Ecuador
| | - Miriann Mora
- PhD Program in Medical Sciences, Universidad de La Frontera, Temuco, Chile.,Faculty of Medicine, Universidad del Azuay, Cuenca, Ecuador
| | - Enmanuel Guerrero
- PhD Program in Medical Sciences, Universidad de La Frontera, Temuco, Chile.,Solca Cancer Institute, Sociedad de Lucha Contra el Cáncer, Cuenca, Ecuador
| | - Nayeli García
- PhD Program in Medical Sciences, Universidad de La Frontera, Temuco, Chile
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13
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Lamminaho M, Kujala J, Peltonen H, Tengström M, Kosma VM, Mannermaa A. High Cell-Free DNA Integrity Is Associated with Poor Breast Cancer Survival. Cancers (Basel) 2021; 13:cancers13184679. [PMID: 34572906 PMCID: PMC8467852 DOI: 10.3390/cancers13184679] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/10/2021] [Accepted: 09/15/2021] [Indexed: 01/16/2023] Open
Abstract
Simple Summary A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and BC survival is already recognized, studies on the prognostic value of cfDI have had contradictory results. The aim of this study was to investigate the prognostic potential of cfDConc and cfDI in Eastern Finnish BC cases with a non-metastatic disease. While the prognostic value of cfDConc remained non-significant in our analyses, high cfDI was an independent prognostic factor for poor overall survival (OS) and breast cancer-specific survival (BCSS). Inclusion of cfDI in the multivariate logistic regression model improved the predictive performance of the model, thus suggesting that the combined use of traditional tumor features and liquid biopsy could help to discriminate BC patients with poor OS and BCSS more accurately at the time of diagnosis. Abstract Background: A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA (cfDNA) and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and poor survival is already recognized, studies on the prognostic value of cfDI have had contradictory results. Here, we provide further evidence to support the use of cfDI as a potential biomarker. Methods: We selected 204 Eastern Finnish BC cases with non-metastatic disease and isolated cfDNA from the serum collected at the time of diagnosis before any treatment was given. The cfDConc and cfDI were measured with a fluorometer and electrophoresis and analyzed with 25 years of survival data. Results: High cfDConc was not an independent prognostic factor in our analyses while high cfDI was found to be an independent prognostic factor for poor OS (p = 0.020, hazard ratio (HR) = 1.57, 95% confidence interval (CI) 1.07–2.29, Cox) and BCSS (p = 0.006, HR = 1.93, 95% CI 1.21–3.08)). Inclusion of cfDI in the multivariate logistic regression model improved the predictive performance. Conclusions: Our results show high cfDI is an independent prognostic factor for poor OS and BCSS and improves the predictive performance of logistic regression models, thus supporting its prognostic potential.
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Affiliation(s)
- Maria Lamminaho
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland; (M.L.); (J.K.); (H.P.); (V.-M.K.)
| | - Jouni Kujala
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland; (M.L.); (J.K.); (H.P.); (V.-M.K.)
| | - Hanna Peltonen
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland; (M.L.); (J.K.); (H.P.); (V.-M.K.)
| | - Maria Tengström
- Cancer Center, Kuopio University Hospital, FI-70029 Kuopio, Finland;
| | - Veli-Matti Kosma
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland; (M.L.); (J.K.); (H.P.); (V.-M.K.)
- Department of Clinical Pathology, Kuopio University Hospital, FI-70029 Kuopio, Finland
- Multidisciplinary Cancer Research Community (RC Cancer), University of Eastern Finland, FI-70211 Kuopio, Finland
- Biobank of Eastern Finland, Kuopio University Hospital, FI-70029 Kuopio, Finland
| | - Arto Mannermaa
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland; (M.L.); (J.K.); (H.P.); (V.-M.K.)
- Multidisciplinary Cancer Research Community (RC Cancer), University of Eastern Finland, FI-70211 Kuopio, Finland
- Biobank of Eastern Finland, Kuopio University Hospital, FI-70029 Kuopio, Finland
- Correspondence:
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14
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The relevance of liquid biopsy in surgical oncology: The application of perioperative circulating nucleic acid dynamics in improving patient outcomes. Surgeon 2021; 20:e163-e173. [PMID: 34362650 DOI: 10.1016/j.surge.2021.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 06/13/2021] [Accepted: 06/23/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND Liquid biopsy is gaining increasing clinical utility in the management of cancer patients. The main components of a liquid biopsy are circulating nucleic acids, circulating tumour cells and extracellular vesicles such as exosomes. Circulating nucleic acids including cell free DNA (cfDNA) and circulating tumour DNA (ctDNA) in particular have been the focus of recent attention as they have demonstrated excellent potential in cancer screening, provision of prognostic information and in genomic profiling of a tumour without the need for repeated tissue biopsies. The aim of this review was to explore the current evidence in relation to the use of liquid biopsy in the perioperative setting and identify ways in which liquid biopsy may be applied in the future. METHODS This narrative review is based on a comprehensive literature search up to the 1st of June 2020 for papers relevant to the application of liquid biopsy in surgical oncology, focusing particularly on the perioperative period. RESULTS Recent evidence has demonstrated that perioperative liquid biopsy can accurately stratify patients' risk of recurrence compared to conventional biomarkers. Attention to the perioperative dynamics of liquid biopsy components can potentially provide new understanding of the complex relationship between surgery and cancer outcome. In addition, careful evaluation of liquid biopsy components in the perioperative window may provide important diagnostic and therapeutic information for cancer patients. CONCLUSION The rapidly evolving concept of the liquid biopsy has the potential to become the cornerstone for decision making around surveillance and adjuvant therapies the era of personalised medicine.
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Li S, Zhang G, Li X, Li X, Chen X, Xu Y, Ren H. Role of the preoperative circulating tumor DNA KRAS mutation in patients with resectable pancreatic cancer. Pharmacogenomics 2021; 22:657-667. [PMID: 34120460 DOI: 10.2217/pgs-2020-0183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: The prognosis of resectable pancreatic cancer patients with the same stage of disease is highly variable. The purpose of this study is to establish a scoring system for preoperative screening of resectable patients. Materials & methods: The clinical information and laboratory tests of 105 resectable patients with pancreatic cancer were enrolled and analyzed. Results: The consistency of clinical stage and pathological stage was poor (κ = 0.193; p < 0.003). We performed a comprehensive scoring system with KRAS mutations in circulating tumor DNA (mutKRAS ctDNA) for the resectable patients. Patients with higher scores were more prone to early postoperative recurrence and poorer prognosis. Conclusion: The scoring system can help preoperatively screen out resectable patients who are prone to early postoperative recurrence.
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Affiliation(s)
- Shengnan Li
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Gengpu Zhang
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Xin Li
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Xiaojie Li
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - XiaoBing Chen
- Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Yu Xu
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.,Department of Oncology, Tianjin Huanghe Hospital, Tianjin, 300060, China
| | - He Ren
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.,Department of Gastroenterology, Center of Tumor Immunology & Cytotherapy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
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Cui R, Wang C, Zhao Q, Wang Y, Li Y. Serum Carboxypeptidase N1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer. Anticancer Agents Med Chem 2021; 20:2053-2065. [PMID: 32619179 DOI: 10.2174/1871520620666200703191135] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Revised: 04/24/2020] [Accepted: 04/25/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND The incidence and mortality of breast cancer are increasing annually. Breast cancer seriously threatens women's health and quality of life. We aimed to measure the clinical value of CPN1, a new serum marker of breast cancer and to evaluate the efficacy of CPN1 in combination with CA15-3. METHODS Seventy samples of breast cancer with lymph node metastasis, seventy-three samples of nonmetastatic breast cancer and twenty-five samples of healthy human serum were collected. Serum CA15-3 concentration was determined by Roche Elecsys, and serum CPN1 concentration was determined by ELISA. RESULTS In breast cancer patients, serum CPN1 concentration was positively correlated with tumour size, clinical stage and CA15-3 concentration (r = 0.376, P<0.0001). ROC curve analysis showed that the optimal critical concentration of CPN1 for breast cancer diagnosis was 32.8pg/ml. The optimal critical concentration of CPN1 in the diagnosis of metastatic breast cancer was 66.121pg/ml. CPN1 has a greater diagnostic ability for breast cancer (AUCCA15-3=0.702 vs. AUCCPN1=0.886, P<0.0001) and metastatic breast cancer (AUCCA15-3=0.629 vs. AUCCPN1=0.887, P<0.0001) than CA15-3, and the combined detection of CA15-3 and CPN1 can improve the diagnostic efficiency for breast cancer (AUCCA15-3+CPN1=0.916) and for distinguishing between metastatic and non-metastatic breast cancer (AUCCA15-3+CPN1=0.895). CONCLUSION CPN1 can be used as a new tumour marker to diagnose and evaluate the invasion and metastasis of breast cancer. The combined detection of CPN1 and CA15-3 is more accurate and has a certain value in clinical application.
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Affiliation(s)
- Ranliang Cui
- Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Chaomin Wang
- Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Qi Zhao
- Tianjin Medical University, Tianjin, China
| | - Yichao Wang
- Department of Clinical Laboratory Medicine, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang Province, China
| | - Yueguo Li
- Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
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Adusei E, Ahenkorah J, Adu-Aryee NA, Adutwum-Ofosu KK, Tagoe EA, Koney NKK, Nkansah E, Aryee NA, Blay RM, Hottor BA, Clegg-Lamptey JN, Arko-Boham B. Reduced Serum Circulation of Cell-Free DNA Following Chemotherapy in Breast Cancer Patients. Med Sci (Basel) 2021; 9:medsci9020037. [PMID: 34070520 PMCID: PMC8163010 DOI: 10.3390/medsci9020037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 05/07/2021] [Accepted: 05/19/2021] [Indexed: 12/21/2022] Open
Abstract
Breast cancer is the most common malignancy in women, with alarming mortalities. Neoadjuvant treatments employ chemotherapy to shrink tumours to a well-defined size for a better surgical outcome. The current means of assessing effectiveness of chemotherapy management are imprecise. We previously showed that breast cancer patients have higher serum circulating cell-free DNA concentrations. cfDNA is degraded cellular DNA fragments released into the bloodstream. We further report on the utility of cfDNA in assessing the response to chemotherapy and its potential as a monitoring biomarker. A total of 32 newly diagnosed and treatment-naive female breast cancer patients and 32 healthy females as controls were included. Anthropometric, demographic and clinicopathological information of participants were recorded. Each participant donated 5 mL of venous blood from which sera were separated. Blood sampling was carried out before the commencement of chemotherapy (timepoint 1) and after the third cycle of chemotherapy (timepoint 2). qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) was determined. ALU 115 and 247 levels were elevated in cancer patients but were significantly decreased after the third cycle of chemotherapy (T2) compared to T1. DNA integrity increased after the third cycle. Serum cfDNA may provide a relatively inexpensive and minimally invasive procedure to evaluate the response to chemotherapy in breast cancer.
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Affiliation(s)
- Evelyn Adusei
- Department of Anatomy, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (E.A.); (J.A.); (K.K.A.-O.); (N.K.-K.K.); (E.N.); (R.M.B.); (B.A.H.)
| | - John Ahenkorah
- Department of Anatomy, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (E.A.); (J.A.); (K.K.A.-O.); (N.K.-K.K.); (E.N.); (R.M.B.); (B.A.H.)
| | - Nii Armah Adu-Aryee
- Department of Surgery, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (N.A.A.-A.); (J.-N.C.-L.)
- Department of Surgery, Korle-Bu Teaching Hospital, Korle Bu, Accra P.O. Box 77, Ghana
| | - Kevin Kofi Adutwum-Ofosu
- Department of Anatomy, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (E.A.); (J.A.); (K.K.A.-O.); (N.K.-K.K.); (E.N.); (R.M.B.); (B.A.H.)
| | - Emmanuel Ayitey Tagoe
- Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, University of Ghana, Accra P.O. Box KB 143, Ghana;
| | - Nii Koney-Kwaku Koney
- Department of Anatomy, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (E.A.); (J.A.); (K.K.A.-O.); (N.K.-K.K.); (E.N.); (R.M.B.); (B.A.H.)
| | - Emmanuel Nkansah
- Department of Anatomy, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (E.A.); (J.A.); (K.K.A.-O.); (N.K.-K.K.); (E.N.); (R.M.B.); (B.A.H.)
| | - Nii Ayite Aryee
- Department of Medical Biochemistry, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana;
| | - Richard Michael Blay
- Department of Anatomy, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (E.A.); (J.A.); (K.K.A.-O.); (N.K.-K.K.); (E.N.); (R.M.B.); (B.A.H.)
| | - Bismarck Afedo Hottor
- Department of Anatomy, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (E.A.); (J.A.); (K.K.A.-O.); (N.K.-K.K.); (E.N.); (R.M.B.); (B.A.H.)
| | - Joe-Nat Clegg-Lamptey
- Department of Surgery, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (N.A.A.-A.); (J.-N.C.-L.)
- Department of Surgery, Korle-Bu Teaching Hospital, Korle Bu, Accra P.O. Box 77, Ghana
| | - Benjamin Arko-Boham
- Department of Anatomy, University of Ghana Medical School, University of Ghana, Accra P.O. Box GP 4236, Ghana; (E.A.); (J.A.); (K.K.A.-O.); (N.K.-K.K.); (E.N.); (R.M.B.); (B.A.H.)
- Correspondence: ; Tel.: +233-200120709
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Circulating Cell-Free DNA in Breast Cancer: Searching for Hidden Information towards Precision Medicine. Cancers (Basel) 2021; 13:cancers13040728. [PMID: 33578793 PMCID: PMC7916622 DOI: 10.3390/cancers13040728] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/05/2021] [Accepted: 02/08/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Our research focuses in the elucidation of the nature of circulating cell-free DNA (ccfDNA) as a biological entity and its exploitation as a liquid biopsy biomaterial. Working on breast cancer, it became clear that although a promising biosource, its clinical exploitation is burdened mainly by gaps in knowledge about its biology and specific characteristics. The current review covers multiple aspects of ccfDNA in breast cancer. We cover key issues such as quantity, integrity, releasing structures, methylation specific changes, release mechanisms, biological role. Machine learning approaches for analyzing ccfDNA-generated data to produce classifiers for clinical use are also discussed. Abstract Breast cancer (BC) is a leading cause of death between women. Mortality is significantly raised due to drug resistance and metastasis, while personalized treatment options are obstructed by the limitations of conventional biopsy follow-up. Lately, research is focusing on circulating biomarkers as minimally invasive choices for diagnosis, prognosis and treatment monitoring. Circulating cell-free DNA (ccfDNA) is a promising liquid biopsy biomaterial of great potential as it is thought to mirror the tumor’s lifespan; however, its clinical exploitation is burdened mainly by gaps in knowledge of its biology and specific characteristics. The current review aims to gather latest findings about the nature of ccfDNA and its multiple molecular and biological characteristics in breast cancer, covering basic and translational research and giving insights about its validity in a clinical setting.
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Tabor S, Szostakowska-Rodzos M, Fabisiewicz A, Grzybowska EA. How to Predict Metastasis in Luminal Breast Cancer? Current Solutions and Future Prospects. Int J Mol Sci 2020; 21:ijms21218415. [PMID: 33182512 PMCID: PMC7665153 DOI: 10.3390/ijms21218415] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 10/28/2020] [Accepted: 11/07/2020] [Indexed: 12/12/2022] Open
Abstract
Breast cancer metastasis is the main cause of breast cancer mortality. Luminal breast cancer represents the majority of breast cancer cases and, despite relatively good prognosis, its heterogeneity creates problems with a proper stratification of patients and correct identification of the group with a high risk of metastatic relapse. Current prognostic tools are based on the analysis of the primary tumor and, despite their undisputed power of prediction, they might be insufficient to foresee the relapse in an accurate and precise manner, especially if the relapse occurs after a long period of dormancy, which is very common in luminal breast cancer. New approaches tend to rely on body fluid analyses, which have the advantage of being non-invasive and versatile and may be repeated and used for monitoring the disease in the long run. In this review we describe the current, newly-developed, and only-just-discovered methods which are or may become useful in the assessment of the probability of the relapse.
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Huang Y, Mu J, Qi L, Ge W, Fang X, Song Y, Yuan Y, Zheng S. Diverse fragment lengths dismiss size selection for serum cell-free DNA: a comparative study of serum and plasma samples. Clin Chem Lab Med 2020; 58:1451-1459. [PMID: 32229658 DOI: 10.1515/cclm-2020-0078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/25/2020] [Indexed: 01/09/2023]
Abstract
Background The objective of this study was to determine the features of fragment length for circulating cell-free DNA (cfDNA) from plasma and serum samples. Methods Plasma and serum samples from different sources were randomly collected. Circulating cfDNA was extracted and purified by a precipitation-enriched and spin-column-based kit. The concentration of the purified DNA was immediately measured by a highly sensitive dsDNA quantitative assay, and then the fragment length was analyzed by capillary electrophoresis. The abundance of a specific fragment was estimated by the area under curve (AUC) for the fragment peak in the capillary electrophoresis. Results A total of 199 plasma and 117 serum samples were extracted and analyzed. The average yield of cfDNA from the serum samples (131.67 ng/mL) was significantly higher than that from the plasma samples (32.78 ng/mL, p < 0.001). The average abundance of the 20-400 bp fragments in plasma cfDNA (84.4%) was significantly higher than that of serum cfDNA (51.9%, p < 0.001). Fragment peaks in serum cfDNA always presented in regions around 190 bp, 430 bp, and 630 bp, but plasma cfDNA generally showed a sharp peak in the 165-190 bp region and a much lower peak in the 300<uni-2013;400 bp region. Large fragments in plasma cfDNA were longer than 1000 bp and peaked around the 3000<uni-2013;4000 bp region while the large fragments in serum cfDNA were always shorter and peaked around the 1000 bp region. Conclusions The fragment lengths of serum cfDNA and plasma cfDNA have very different features. Fragment size selection is suitable for plasma cfDNA but may not apply to serum cfDNA.
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Affiliation(s)
- Yanqin Huang
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P.R. China
| | - Jiayi Mu
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P.R. China
| | - Lina Qi
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P.R. China
| | - Weiting Ge
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P.R. China
| | - Xuefeng Fang
- Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
| | - Yongmao Song
- Department of Colorectal Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang,P.R. China
| | - Ying Yuan
- Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
| | - Shu Zheng
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road,Hangzhou, Zhejiang Province,P.R. China, Phone: +8657187784501, Fax: +8657187214404
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Tuchalska-Czuroń J, Lenart J, Augustyniak J, Durlik M. Clinical value of tissue DNA integrity index in pancreatic cancer. Surgeon 2020; 18:269-279. [PMID: 32156475 DOI: 10.1016/j.surge.2019.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 10/08/2019] [Accepted: 10/28/2019] [Indexed: 10/24/2022]
Abstract
BACKGROUND DNA integrity index as a blood biomarker is associated with the prognosis of cancer patients. AIMS The primary goal of the study was to examine tissue DNA integrity index (DII) in a group of pancreatic cancer (PC) tumor tissues and control adjacent pancreatic tissues. We also aimed to test the relationship between the tumor tissue DII and the clinicopathological parameters and the overall survival. METHODS In the prospective study, DII was calculated using: the Alu 247/115 ratio, the LINE1 300/79 ratio and the average of the above values, based on the data obtained by real-time PCR. The tumors samples (n = 42) originated from the patients with pathologically confirmed pancreatic ductal adenocarcinoma and the control adjacent pancreatic tissue specimens (n = 32) were received from surgical margins. RESULTS Specimens from the tumors pathologically marked as R1 (microscopic residual tumor) had a significantly higher LINE1 300/79 ratio values than specimens from adjacent normal pancreatic tissue (P<0.05). ROC curve analysis revealed that LINE1 300/79 ratio is a good parameter to distinguish between R0 and R1 tumors (AUC = 0.703, P<0.05). CONCLUSIONS This is the first study exploring the tissue DNA integrity index (DII) in pancreatic cancer. LINE1 DII can be used as auxiliary parameter for objective evaluation of margin status.
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Affiliation(s)
- Julia Tuchalska-Czuroń
- Department of Surgical Research and Transplantology, Medical Research Centre Polish Academy of Sciences, Warsaw, Poland; Diagnostic Radiology Department, Central Clinical Hospital of the MSWiA in Warsaw, Poland.
| | - Jacek Lenart
- Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
| | - Justyna Augustyniak
- Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
| | - Marek Durlik
- Department of Surgical Research and Transplantology, Medical Research Centre Polish Academy of Sciences, Warsaw, Poland; Department of Gastroenterological Surgery and Transplantation Medicine, Centre of Postgraduate Medical Education, Warsaw, Poland; Clinical Department of Gastroenterological Surgery and Transplantation Medicine, Central Clinical Hospital of the MSWiA in Warsaw, Poland
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da Silva JL, Cardoso Nunes NC, Izetti P, de Mesquita GG, de Melo AC. Triple negative breast cancer: A thorough review of biomarkers. Crit Rev Oncol Hematol 2019; 145:102855. [PMID: 31927455 DOI: 10.1016/j.critrevonc.2019.102855] [Citation(s) in RCA: 142] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 12/01/2019] [Accepted: 12/02/2019] [Indexed: 02/08/2023] Open
Abstract
Triple-negative breast cancer (TNBC) is defined as a type of breast cancer with lack of expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 protein. The tumorigenesis is not likely to be driven by hormonal or HER2 pathway. In comparison to other types of breast cancer, TNBC stands out for its aggressive behavior, more prone to early recurrence. Historically, TNBC has been considered a disease with poor response to molecular target therapy, requiring better validation of biomarkers. Recent issues related to tumor heterogeneity have been widely discussed suggesting the subdivision of TNBC into different molecular subtypes. Through a complete research on the main published trials databases and platforms of ongoing clinical studies, the current manuscript was carried out in order to present a critical view of the role of immunohistochemical and molecular biomarkers for the prognosis and response prediction of TNBC to traditional therapy and new molecular target agents.
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Cervena K, Vodicka P, Vymetalkova V. Diagnostic and prognostic impact of cell-free DNA in human cancers: Systematic review. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2019; 781:100-129. [PMID: 31416571 DOI: 10.1016/j.mrrev.2019.05.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 05/03/2019] [Accepted: 05/07/2019] [Indexed: 02/06/2023]
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Advances in liquid biopsy using circulating tumor cells and circulating cell-free tumor DNA for detection and monitoring of breast cancer. Clin Exp Med 2019; 19:271-279. [PMID: 31190187 DOI: 10.1007/s10238-019-00563-w] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Accepted: 06/03/2019] [Indexed: 12/17/2022]
Abstract
Overview the progress of liquid biopsy using circulating tumor cells (CTCs) and circulating cell-free tumor DNA (cfDNA) to detect and monitor breast cancer. Based on numerous research efforts, the potential value of CTCs and cfDNA in the clinical aspects of cancer has become clear. With the development of next-generation sequencing analysis and newly developed technologies, many technical issues have been resolved, making liquid biopsy widely used in clinical practice. They can be powerful tools for dynamic monitoring of tumor progression and therapeutic efficacy. In the field of breast cancer, liquid biopsy is a research hot spot in recent years, playing a key role in monitoring breast cancer metastasis, predicting disease recurrence and assessing clinical drug resistance. Liquid biopsy has the advantages of noninvasive, high sensitivity, high specificity and real-time dynamic monitoring. Still application is far from reality, but the research and application prospects of CTCs and cfDNA in breast cancer are still worth exploring and discovering. This article reviews the main techniques and applications of CTCs and cfDNA in breast cancer.
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Arko-Boham B, Aryee NA, Blay RM, Owusu EDA, Tagoe EA, Doris Shackie ES, Debrah AB, Adu-Aryee NA. Circulating cell-free DNA integrity as a diagnostic and prognostic marker for breast and prostate cancers. Cancer Genet 2019; 235-236:65-71. [PMID: 31105051 DOI: 10.1016/j.cancergen.2019.04.062] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 04/15/2019] [Accepted: 04/21/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Cancer incidence and its related mortality is rising and is currently the second leading cause of death globally. In Africa, breast and prostate cancer in females and males, respectively, are the worst globally. However, biomarkers for their early detection and prognosis are not well developed. This study sought to investigate circulating cell-free DNA (ccfDNA) integrity and its potential utility as diagnostic and/or prognostic biomarker. Circulating cell-free DNA (ccfDNA) is degraded DNA fragments released into the blood plasma. In healthy individuals, the source of ccfDNA is solely apoptosis, producing evenly sized shorter DNA fragments. In cancer patients, however, necrosis produces uneven longer cell-free DNA fragments in addition to the shorter fragments originating from apoptosis. DNA integrity, expressed as the ratio of longer fragments to total DNA, may be clinically useful for the detection of breast and prostate cancer progression. METHODS Sixty-four (64) females, consisting of 32 breast cancer patients and 32 controls, and 61 males (31 prostate cancer patients and 30 controls) were included in the study. Each participant donated 5 ml peripheral blood from which sera were separated. Real-time qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) determined. RESULTS & CONCLUSION ALU species 115 and 247 levels in serum were elevated in breast and prostate cancer patients compared to their counterpart healthy controls. DNA integrity was higher in prostate cancer patients than in the control, but in breast cancer patients was lower compared to their controls. In prostate but not in breast cancers, DNA integrity increased with disease severity and higher staging.
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Affiliation(s)
- Benjamin Arko-Boham
- Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana; Department of Anatomy, School of Biomedical and Allied Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana.
| | - Nii Ayite Aryee
- Department of Medical Biochemistry, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana
| | - Richard Michael Blay
- Department of Anatomy, School of Biomedical and Allied Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana
| | - Ewurama Dedea Ampadu Owusu
- Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana; Centre of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Centre, University of Amsterdam, Postbus 226601100 DD Amsterdam, the Netherlands; Foundation for Innovative and New Diagnostics (FIND), 9 Chemin des Mines, 1202, Geneva, Switzerland
| | - Emmanuel Ayitey Tagoe
- Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana; West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, P.O. Box LG 25, Legon, Accra, Ghana
| | - Eshirow-Sam Doris Shackie
- Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana
| | - Ama Boatemaa Debrah
- Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana
| | - Nii Armah Adu-Aryee
- Department of Surgery, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana; Department of Surgery, Korle-Bu Teaching Hospital, P.O. Box, 77 Accra, Ghana
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Potential Utility of Liquid Biopsy as a Diagnostic and Prognostic Tool for the Assessment of Solid Tumors: Implications in the Precision Oncology. J Clin Med 2019; 8:jcm8030373. [PMID: 30889786 PMCID: PMC6463095 DOI: 10.3390/jcm8030373] [Citation(s) in RCA: 87] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 02/24/2019] [Accepted: 03/13/2019] [Indexed: 02/07/2023] Open
Abstract
Liquid biopsy is a technique that utilizes circulating biomarkers in the body fluids of cancer patients to provide information regarding the genetic landscape of the cancer. It is emerging as an alternative and complementary diagnostic and prognostic tool to surgical biopsy in oncology. Liquid biopsy focuses on the detection and isolation of circulating tumor cells, circulating tumor DNA and exosomes, as a source of genomic and proteomic information in cancer patients. Liquid biopsy is expected to provide the necessary acceleratory force for the implementation of precision oncology in clinical settings by contributing an enhanced understanding of tumor heterogeneity and permitting the dynamic monitoring of treatment responses and genomic variations. However, widespread implementation of liquid biopsy based biomarker-driven therapy in the clinical practice is still in its infancy. Technological advancements have resolved many of the hurdles faced in the liquid biopsy methodologies but sufficient clinical and technical validation for specificity and sensitivity has not yet been attained for routine clinical implementation. This article provides a comprehensive review of the clinical utility of liquid biopsy and its effectiveness as an important diagnostic and prognostic tool in colorectal, breast, hepatocellular, gastric and lung carcinomas which were the five leading cancer related mortalities in 2018.
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Shang M, Chang C, Pei Y, Guan Y, Chang J, Li H. Potential Management of Circulating Tumor DNA as a Biomarker in Triple-Negative Breast Cancer. J Cancer 2018; 9:4627-4634. [PMID: 30588246 PMCID: PMC6299380 DOI: 10.7150/jca.28458] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 09/11/2018] [Indexed: 12/18/2022] Open
Abstract
As a specific subtype of breast cancer, Triple-negative breast cancer (TNBC) is associated with worse prognosis and higher tumor aggressiveness than HER2-amplified or hormone receptor positive breast cancers. Circulating tumor DNA (ctDNA), as a non-invasive “liquid biopsy”, is an emerging original blood-based biomarker for early breast cancer diagnosis, monitoring treatment response, and determining prognosis. In TNBC patients, ctDNA has an inherent tendency to characterize tumor heterogeneity and metastasis-specific mutations providing a key alternative to tumor tissue profiling. Several studies have already demonstrated the potential of ctDNA in TNBC patients from early to advanced stages of the disease including diagnosis, therapy decisions and assessment of prognosis. This review provides a critical brief summary of the evidence that gives credence to the utility of ctDNA as a biomarker for its role into clinical management in TNBC.
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Affiliation(s)
- Mao Shang
- School of Medicine and Life Sciences, University of Jinan Shandong Academy of Medical Sciences, Jinan, Shandong, China.,Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China. 250117
| | - Chunxiao Chang
- Department of Medical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China. 250117
| | - Yanqing Pei
- Department of Quality Management Office, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China. 250117
| | - Yin Guan
- Department of Medical Oncology, Beijing Chao-Yang Hospital, Beijing, China
| | - Jin Chang
- Oncology department, Affiliated Hospital of Taishan Medical university
| | - HuiHui Li
- Department of Medical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China. 250117
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Lee JH, Jeong H, Choi JW, Oh HE, Kim YS. Liquid biopsy prediction of axillary lymph node metastasis, cancer recurrence, and patient survival in breast cancer: A meta-analysis. Medicine (Baltimore) 2018; 97:e12862. [PMID: 30334995 PMCID: PMC6211877 DOI: 10.1097/md.0000000000012862] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Liquid biopsies using circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) have been developed for early cancer detection and patient monitoring. To investigate the clinical usefulness of ctDNA aberrations and cfDNA levels in patients with breast cancer (BC), we conducted a meta-analysis of 69 published studies on 5736 patients with BC. METHODS The relevant publications were identified by searching PubMed and Embase databases. The effect sizes of outcome parameters were pooled using a random-effects model. RESULTS The ctDNA mutation rates of TP53, PIK3CA, and ESR1 were approximately 38%, 27%, and 32%, respectively. High levels of cfDNA were associated with BCs rather than with healthy controls. However, these detection rates were not satisfactory for BC screening. Although the precise mechanisms have been unknown, high cfDNA levels were significantly associated with axillary lymph node metastasis (odds ratio [OR] = 2.148, P = .030). The ctDNA mutations were significantly associated with cancer recurrence (OR = 3.793, P < .001), short disease-free survival (univariate hazard ratio [HR] = 5.180, P = .026; multivariate HR = 3.605, P = .001), and progression-free survival (HR = 1.311, P = .013) rates, and poor overall survival outcomes (HR = 2.425, P = .007). CONCLUSION This meta-analysis demonstrates that ctDNA mutation status predicts disease recurrence and unfavorable survival outcomes, while cfDNA levels can be predictive of axillary lymph node metastasis in patients with BC.
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Yang J, Cheng L, Zhang J, Chen L, Wang D, Guo X, Ma X. Predictive value of circulating cell-free DNA in the survival of breast cancer patients: A systemic review and meta-analysis. Medicine (Baltimore) 2018; 97:e11417. [PMID: 29995790 PMCID: PMC6076113 DOI: 10.1097/md.0000000000011417] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Accepted: 06/11/2018] [Indexed: 02/05/2023] Open
Abstract
PURPOSE Circulating cell-free DNA (cfDNA) has been reported to predict outcomes in patients with various types of cancer. However, its prognostic value in patients with breast cancer is not well established still now. In this meta-analysis, we evaluated the prognostic role of cfDNA in breast cancer patients. METHODS We performed systematic searches in electronic databases to identify studies that evaluated the prognostic value of cfDNA in breast cancer patients. The end points were progression-free survival (PFS) and overall survival (OS). The hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were extracted to assess the prognostic significance of cfDNA. Subgroup analyses were also conducted. RESULTS A total of 11 publications involving 1467 patients were included in this meta-analysis. cfDNA was shown to be significantly associated with PFS (HR 2.02, 95% CI 1.51-2.72, P < .001, I = 82%) and OS (HR 1.75, 95% CI 1.01-3.05, P < .001, I = 92%). The results of subgroup analyses also revealed that cfDNA was a good predictor of prognosis in breast cancer patients. CONCLUSION Our meta-analysis indicated that cfDNA was associated with poor PFS and OS, thus it may help to predict outcomes of patients with breast cancer. However, further studies are needed to confirm our results.
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Affiliation(s)
- Jing Yang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu West China School of Stomatology Sichuan University, Chengdu, China
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Sobhani N, Generali D, Zanconati F, Bortul M, Scaggiante B. Cell-free DNA integrity for the monitoring of breast cancer: Future perspectives? World J Clin Oncol 2018; 9:26-32. [PMID: 29651384 PMCID: PMC5893994 DOI: 10.5306/wjco.v9.i2.26] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 02/02/2018] [Accepted: 03/14/2018] [Indexed: 02/06/2023] Open
Abstract
Breast cancer (BC) is the most common cancer and the second cause of death in women worldwide. Therapeutic options are increasing, but the response to treatments is not always efficient and the risk of recurrence covers decades. In this perspective, the need to have a proper follow-up for the therapeutic responses and for anticipating recurrence it is urgent in the clinical setting. Liquid biopsy provides the basic principle for a non-invasive method for the routinely monitoring of BC. However, due to the heterogeneity of tumors during onset and progression, the search for tumor DNA mutations of targeted genes in plasma/serum is a limiting factor. A possible approach overtaking this problem comes from the measurement of cell-free DNA integrity, which is an independent factor from the mutational status and theoretically is representative of all tumors. This review summarizes the state-of-the-art of cell-free DNA integrity researches in BC, the controversies and the future perspective.
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Affiliation(s)
- Navid Sobhani
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, Trieste 34149, Italy
| | - Daniele Generali
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, Trieste 34149, Italy
| | - Fabrizio Zanconati
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, Trieste 34149, Italy
| | - Marina Bortul
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, Trieste 34149, Italy
| | - Bruna Scaggiante
- Department of Life Sciences, University of Trieste, Trieste 34127, Italy
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Value of circulating cell-free DNA analysis as a diagnostic tool for breast cancer: a meta-analysis. Oncotarget 2018; 8:26625-26636. [PMID: 28460452 PMCID: PMC5432284 DOI: 10.18632/oncotarget.15775] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 02/15/2017] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES The aim of this study was to systematically evaluate the diagnostic value of cell free DNA (cfDNA) for breast cancer. RESULTS Among 308 candidate articles, 25 with relevant diagnostic screening qualified for final analysis. The mean sensitivity, specificity and area under the curve (AUC) of SROC plots for 24 studies that distinguished breast cancer patients from healthy controls were 0.70, 0.87, and 0.9314, yielding a DOR of 32.31. When analyzed in subgroups, the 14 quantitative studies produced sensitivity, specificity, AUC, and a DOR of 0.78, 0.83, 0.9116, and 24.40. The 10 qualitative studies produced 0.50, 0.98, 0.9919, and 68.45. For 8 studies that distinguished malignant breast cancer from benign diseases, the specificity, sensitivity, AUC and DOR were 0.75, 0.79, 0.8213, and 9.49. No covariate factors had a significant correlation with relative DOR. Deek's funnel plots indicated an absence of publication bias. MATERIALS AND METHODS Databases were searched for studies involving the use of cfDNA to diagnose breast cancer. The studies were analyzed to determine sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the summary receiver operating characteristic (SROC). Covariates were evaluated for effect on relative DOR. Deek's Funnel plots were generated to measure publication bias. CONCLUSIONS Our analysis suggests a promising diagnostic potential of using cfDNA for breast cancer screening, but this diagnostic method is not yet independently sufficient. Further work refining qualitative cfDNA assays will improve the correct diagnosis of breast cancers.
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Abstract
BACKGROUND Circulating cell-free DNA (cfDNA) isolated from plasma or serum by noninvasive procedures can serve as a "liquid biopsy" and has potential as a biomarker for the tumor burden and survival prediction of breast cancer (BC). However, its prognostic value in patients with BC is currently under debate. The aim of this meta-analysis was to investigate the relationship between cfDNA and survival outcome. METHODS We systematically searched PubMed, Embase, and Science Citation Index electronic databases for studies about the prognostic utility of cfDNA in patients with BC. The clinical characteristics, relapse/disease-free survival (RFS/DFS), and overall survival (OS) data were extracted from the eligible studies. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated and pooled with a fixed-effects model using the Stata12.0 software. Subgroup and sensitivity analyses were also performed. RESULTS This meta-analysis included a total of 10 eligible studies and 1127 patients with BC. The pooled HR with 95% CI showed strong associations between cfDNA and OS (HR = 2.41, 95% CI, 1.83-3.16) along with DFS/RFS (HR = 2.73, 95% CI, 2.04-3.67) in patients with BC. Although publication bias was found in the studies regarding RFS/DFS, further trim and fill analysis revealed that the adjusted HR would be 2.53 (95% CI, 1.83-3.51), which is close to the original HR. Subgroup analyses confirmed the role of cfDNA as a strong prognostic marker in patients with BC, regardless of cfDNA analysis, sampling time, sample source, detection method, tumor stage, sample size, or area. CONCLUSIONS Our meta-analysis indicates that cfDNA is a strong predictive and prognostic marker in patients with BC.
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Affiliation(s)
| | - Chang Chu
- Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, People's Republic of China
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Hench IB, Hench J, Tolnay M. Liquid Biopsy in Clinical Management of Breast, Lung, and Colorectal Cancer. Front Med (Lausanne) 2018; 5:9. [PMID: 29441349 PMCID: PMC5797586 DOI: 10.3389/fmed.2018.00009] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 01/15/2018] [Indexed: 12/12/2022] Open
Abstract
Examination of tumor molecular characteristics by liquid biopsy is likely to greatly influence personalized cancer patient management. Analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor-derived exosomes, all collectively referred to as “liquid biopsies,” are not only a modality to monitor treatment efficacy, disease progression, and emerging therapy resistance mechanisms, but they also assess tumor heterogeneity and evolution in real time. We review the literature concerning the examination of ctDNA and CTC in a diagnostic setting, evaluating their prognostic, predictive, and monitoring capabilities. We discuss the advantages and limitations of various leading ctDNA/CTC analysis technologies. Finally, guided by the results of clinical trials, we discuss the readiness of cell-free DNA and CTC as routine biomarkers in the context of various common types of neoplastic disease. At this moment, one cannot conclude whether or not liquid biopsy will become a mainstay in oncology practice.
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Affiliation(s)
- Ivana Bratić Hench
- Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
| | - Jürgen Hench
- Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
| | - Markus Tolnay
- Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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Park K, Woo M, Kim JE, Ahn JH, Jung KH, Roh J, Gong G, Kim SB. Efficacy of assessing circulating cell-free DNA using a simple fluorescence assay in patients with triple-negative breast cancer receiving neoadjuvant chemotherapy: a prospective observational study. Oncotarget 2017; 9:3875-3886. [PMID: 29423090 PMCID: PMC5790507 DOI: 10.18632/oncotarget.23520] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 11/15/2017] [Indexed: 12/31/2022] Open
Abstract
This study aims to assess cell-free DNA (CFD) by a fluorescence assay as a biomarker for early prediction of a pathologic complete response (pCR) and relapse in patients with triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy. Patients with clinical stage II or III TNBC scheduled for neoadjuvant chemotherapy were prospectively enrolled. All patients underwent four cycles of Adriamycin plus cyclophosphamide (AC), followed by four cycles of cisplatin or docetaxel chemotherapy and surgery. Blood samples were obtained before the initial chemotherapy (baseline-CFD) and after four AC neoadjuvant chemotherapy cycles (AC-CFD) to evaluate CFD levels. In total, 72 patients who met the inclusion criteria were enrolled. The mean baseline-CFD and AC-CFD levels were 239 ± 68 and 210 ± 66 ng/mL, respectively, with a significant decline in the CFD levels after AC neoadjuvant chemotherapy (P = 0.001). In the 33.6-month median follow-up, 18 cases of relapse were reported. A ROC curve analysis of baseline-CFD was performed to determine the predictive value for relapse, and an area under the curve of 0.62 (95% CI, 0.46–0.78) at 264 ng/mL was obtained. Patients with baseline-CFD >264 ng/mL were at a higher risk of relapse than those with baseline-CFD ≤264 ng/mL (HR, 2.84; 95% CI, 1.11–7.24; P = 0.029). Multivariate analysis established baseline-CFD as an independent predicting factor for relapse (HR, 3.74; 95% CI, 1.32–10.53; P = 0.013). In conclusion, baseline-CFD measured by a fluorescence assay might be a potential biomarker to predict relapse, which could be useful for risk stratification of TNBC.
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Affiliation(s)
- Kwonoh Park
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Medical Oncology and Hematology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan-si, Republic of Korea
| | - Miyoung Woo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jeong Eun Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin-Hee Ahn
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kyung Hae Jung
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin Roh
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Gyungyub Gong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Bae Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Chiodi I, Scovassi AI, Mondello C. Circulating Molecular and Cellular Biomarkers in Cancer. TRANSLATIONAL TOXICOLOGY AND THERAPEUTICS: WINDOWS OF DEVELOPMENTAL SUSCEPTIBILITY IN REPRODUCTION AND CANCER 2017:607-656. [DOI: 10.1002/9781119023647.ch16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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36
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Chang Y, Tolani B, Nie X, Zhi X, Hu M, He B. Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring. Ther Clin Risk Manag 2017; 13:1363-1374. [PMID: 29066904 PMCID: PMC5644666 DOI: 10.2147/tcrm.s141991] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Circulating cell-free DNA (cfDNA) released by tumor cells, termed ctDNA, closely reflects the heterogeneity of primary cancers and their metastases. As a noninvasive, real-time monitoring biomarker, ctDNA is a promising tool for detecting driver gene mutations, assessing tumor burden and acquired resistance, and early diagnosis. However, isolation and enrichment of cfDNA is a big challenge due to the high degree of DNA fragmentation and its relatively low abundance in the bloodstream. This review aims to provide insights into the recent technological advances in acquisition of optimal quality cfDNA, the use of preservatives, isolation methods, processing timelines, and detection techniques. It also describes clinical applications of ctDNA in cancer patient management.
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Affiliation(s)
- Yi Chang
- Department of Respiratory Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
- Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA
| | - Bhairavi Tolani
- Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA
| | - Xiuhong Nie
- Department of Respiratory Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xiuyi Zhi
- Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Mu Hu
- Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Biao He
- Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA
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Cytosolic THUMPD1 promotes breast cancer cells invasion and metastasis via the AKT-GSK3-Snail pathway. Oncotarget 2017; 8:13357-13366. [PMID: 28076326 PMCID: PMC5355103 DOI: 10.18632/oncotarget.14528] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 12/27/2016] [Indexed: 01/05/2023] Open
Abstract
Human THUMP domain-containing protein 1 (THUMPD1) is a specific adaptor protein that modulates tRNA acetylation through interaction with NAT10. Immunohistochemical analysis of 146 breast cancer specimens (82 triple-negative and 64 non-triple-negative cases) indicated THUMPD1 expression is higher in breast cancer tissues (60.9%, 89/146) than normal breast tissues (28.3%, 15/53; p < 0.001). Overall and cytosolic, but not nuclear, THUMPD1 expression in breast cancer correlated with advanced TNM stage (p = 0.003 and p < 0.001, respectively), lymph node metastasis (p = 0.001 and p < 0.001, respectively), and poor patient prognosis (p = 0.001 and p < 0.001, respectively). THUMPD1 interacted and co-localized with YAP, but did not affect Hippo pathway activity. THUMPD1 overexpression enhanced breast cancer cells invasion and migration in vivo and in vitro, possibly through activation of AKT, GSK3β and Snail, and inhibition of E-cadherin. Treatment with the AKT inhibitor, LY294002, reduced the effects of THUMPD1 overexpression in breast cancer cells. These results indicate that THUMPD1 promotes breast cancer cells invasion and migration via the AKT-GSK3β-Snail pathway.
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Integrity and Quantity of Total Cell-Free DNA in the Diagnosis of Thyroid Cancer: Correlation with Cytological Classification. Int J Mol Sci 2017; 18:ijms18071350. [PMID: 28672797 PMCID: PMC5535843 DOI: 10.3390/ijms18071350] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Revised: 06/19/2017] [Accepted: 06/22/2017] [Indexed: 01/04/2023] Open
Abstract
Cell-free DNA (cfDNA) quantity and quality in plasma has been investigated as a non-invasive biomarker in cancer. Previous studies have demonstrated increased cfDNA amount and length in different types of cancer with respect to healthy controls. The present study aims to test the hypothesis that the presence of longer DNA strands circulating in plasma can be considered a biomarker for tumor presence in thyroid cancer. We adopted a quantitative real-time PCR (qPCR) approach based on the quantification of two amplicons of different length (67 and 180 bp respectively) to evaluate the integrity index 180/67. Cell-free DNA quantity and integrity were higher in patients affected by nodular thyroid diseases than in healthy controls. Importantly, cfDNA integrity index was higher in patients with cytological diagnosis of thyroid carcinoma (Thy4/Thy5) than in subjects with benign nodules (Thy2). Therefore, cfDNA integrity index 180/67 is a suitable parameter for monitoring cfDNA fragmentation in thyroid cancer patients and a promising circulating biomarker in the diagnosis of thyroid nodules.
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Cheng J, Cuk K, Heil J, Golatta M, Schott S, Sohn C, Schneeweiss A, Burwinkel B, Surowy H. Cell-free circulating DNA integrity is an independent predictor of impending breast cancer recurrence. Oncotarget 2017; 8:54537-54547. [PMID: 28903362 PMCID: PMC5589601 DOI: 10.18632/oncotarget.17384] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 03/26/2017] [Indexed: 12/14/2022] Open
Abstract
Non-invasive blood-based molecule markers are evaluated as promising biomarkers these days. Here we investigated the potential of cell-free circulating DNA Integrity (cfDI) as blood-based marker for the prediction of recurrence during the follow-up of breast cancer patients within a prospective study cohort. cfDI was determined in plasma of 212 individuals, by measuring ALU and LINE1 repetitive DNA elements using quantitative PCR. A significant decrease of cfDI in recurrent breast cancer patients was observed. The group of patients who had impending recurrence during the follow-up had significant lower cfDI compared to the group of non-recurrent patients (P < 0.001 for ALU and LINE1 cfDI). cfDI could differentiate recurrent breast cancer patients from non-recurrent breast cancer subjects (area under the curve, AUC = 0.710 for ALU and 0.704 for LINE1). Univariate and multivariate analysis confirmed a significant association of recurrence and cfDI. Breast cancer patients with a lower cfDI had a much higher risk to develop recurrence than the patients with a higher cfDI (P = 0.020 for ALU cfDI and P = 0.019 for LINE1 cfDI, respectively). Further we show that cfDI is an independent predictor of breast cancer recurrence. In combination with other molecular markers, cfDI might be a useful biomarker for the prediction for breast cancer recurrence in clinic utility. We propose that cfDI might also be useful for the prediction of recurrence during the follow-up of other cancers.
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Affiliation(s)
- Jie Cheng
- Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany
| | - Katarina Cuk
- Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany
| | - Jörg Heil
- Department of Gynecology and Obstetrics, University Women's Clinic, Heidelberg, Germany
| | - Michael Golatta
- Department of Gynecology and Obstetrics, University Women's Clinic, Heidelberg, Germany
| | - Sarah Schott
- Department of Gynecology and Obstetrics, University Women's Clinic, Heidelberg, Germany
| | - Christof Sohn
- Department of Gynecology and Obstetrics, University Women's Clinic, Heidelberg, Germany
| | - Andreas Schneeweiss
- Department of Gynecology and Obstetrics, University Women's Clinic, Heidelberg, Germany.,National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
| | - Barbara Burwinkel
- Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany
| | - Harald Surowy
- Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany
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Botnariuc I, Ilie S, Trifanescu O, Bacinschi X, Curea F, Anghel R. PREDICTIVE CIRCULATING MARKERS FOR ANTHRACYCLINE CHEMOTHERAPY IN NON-METASTATIC BREAST CANCER. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2017; 13:209-214. [PMID: 31149175 PMCID: PMC6516453 DOI: 10.4183/aeb.2017.209] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Anthracyclines are used in breast cancer both in early and advanced stages and their recommendation together with taxanes, either concurrently or sequentially, is debatable and individualized by phenotype. Circulating biomarkers have already been introduced in clinical practice for metastatic disease monitoring. We questioned whether it might be a role for these markers in neoadjuvant and adjuvant settings too and a general review was conducted. CK18 and CTC were found predictive for anthracycline related response in preoperative setting. Soluble E-cadherin is promising, a retrospective analysis showing a direct correlation with clinical response. CEA, CA 15-3 and HER2 ECD are not of interest for their predictive role.
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Affiliation(s)
- I. Botnariuc
- “Alexandru Trestioreanu” Institute of Oncology, Ringgold Standard Institution, Dept. of Radiotherapy, Bucharest, Romania
| | - S.M. Ilie
- “Alexandru Trestioreanu” Institute of Oncology, Ringgold Standard Institution, Dept. of Radiotherapy, Bucharest, Romania
| | - O.G. Trifanescu
- “Alexandru Trestioreanu” Institute of Oncology, Ringgold Standard Institution, Dept. of Radiotherapy, Bucharest, Romania
| | - X.E. Bacinschi
- “Alexandru Trestioreanu” Institute of Oncology, Ringgold Standard Institution, Dept. of Radiotherapy, Bucharest, Romania
| | - F. Curea
- “Alexandru Trestioreanu” Institute of Oncology, Ringgold Standard Institution, Dept. of Radiotherapy, Bucharest, Romania
| | - R.M. Anghel
- “Alexandru Trestioreanu” Institute of Oncology, Ringgold Standard Institution, Dept. of Radiotherapy, Bucharest, Romania
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Alekseeva LA, Mironova NL, Brenner EV, Kurilshikov AM, Patutina OA, Zenkova MA. Alteration of the exDNA profile in blood serum of LLC-bearing mice under the decrease of tumour invasion potential by bovine pancreatic DNase I treatment. PLoS One 2017; 12:e0171988. [PMID: 28222152 PMCID: PMC5319761 DOI: 10.1371/journal.pone.0171988] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 01/30/2017] [Indexed: 12/20/2022] Open
Abstract
Taking into account recently obtained data indicating the participation of circulating extracellular DNA (exDNA) in tumorigenesis, enzymes with deoxyribonucleic activity have again been considered as potential antitumour and antimetastatic drugs. Previously, using murine Lewis lung carcinoma and hepatocellular carcinoma A1 tumour models, we have shown the antimetastatic activity of bovine DNase I, which correlates with an increase of DNase activity and a decrease of exDNA concentration in the blood serum of tumour-bearing mice. In this work, using next-generation sequencing on the ABS SOLiD™ 5.500 platform, we performed a search for molecular targets of DNase I by comparing the exDNA profiles of healthy animals, untreated animals with Lewis lung carcinoma (LLC) and those with LLC treated with DNase I. We found that upon DNase I treatment of LLC-bearing mice, together with inhibition of metastasis, a number of strong alterations in the patterns of exDNA were observed. The major differences in exDNA profiles between groups were: i) the level of GC-poor sequences increased during tumour development was reduced to that of healthy mice; ii) levels of sequences corresponding to tumour-associated genes Hmga2, Myc and Jun were reduced in the DNase I-treated group in comparison with non-treated mice; iii) 224 types of tandem repeat over-presented in untreated LLC-bearing mice were significantly reduced after DNase I treatment. The most important result obtained in the work is that DNase I decreased the level of B-subfamily repeats having homology to human ALU repeats, known as markers of carcinogenesis, to the level of healthy animals. Thus, the obtained data lead us to suppose that circulating exDNA plays a role in tumour dissemination, and alteration of multiple molecular targets in the bloodstream by DNase I reduces the invasive potential of tumours.
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Affiliation(s)
- Ludmila A. Alekseeva
- Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia
| | - Nadezhda L. Mironova
- Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia
| | - Evgenyi V. Brenner
- Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia
| | | | - Olga A. Patutina
- Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia
| | - Marina A. Zenkova
- Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia
- * E-mail:
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Beffagna G, Sammarco A, Bedin C, Romualdi C, Mainenti M, Mollo A, Cavicchioli L, Ferro S, Trez D, De Maria R, Nitti D, Saccani A, Campanella M, Agostini M, Zappulli V. Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index. PLoS One 2017; 12:e0169454. [PMID: 28081183 PMCID: PMC5231265 DOI: 10.1371/journal.pone.0169454] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 12/16/2016] [Indexed: 02/06/2023] Open
Abstract
Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs. The cfDNA fragments and integrity index significantly differentiated neoplastic versus non-neoplastic dogs (P<0.05), and allowed the distinction between benign and malignant lesions (P<0.05). Even if without statistical significance, the amount of cfDNA was also affected by tumor necrosis and correlated with tumor size and apoptotic markers expression. A significant (P<0.01) increase of Bcl-2 in malignant tumors was observed, and in metastatic CMTs the evasion of apoptosis was also suggested. This study, therefore, provides evidence that cfDNA could be a diagnostic marker in dogs carrying mammary nodules suggesting that its potential application in early diagnostic procedures should be further investigated.
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Affiliation(s)
- Giorgia Beffagna
- Department of Comparative Biomedicine and Food Science, University of Padua, Legnaro, Padua, Italy
| | - Alessandro Sammarco
- Department of Comparative Biomedicine and Food Science, University of Padua, Legnaro, Padua, Italy
| | - Chiara Bedin
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
- Istituto di Ricerca Pediatrica – Città della Speranza, Padua, Italy
| | | | - Marta Mainenti
- Department of Comparative Biomedicine and Food Science, University of Padua, Legnaro, Padua, Italy
| | - Antonio Mollo
- Department of Animal Medicine, Productions and Health, University of Padua, Legnaro, Padua, Italy
| | - Laura Cavicchioli
- Department of Comparative Biomedicine and Food Science, University of Padua, Legnaro, Padua, Italy
| | - Silvia Ferro
- Department of Comparative Biomedicine and Food Science, University of Padua, Legnaro, Padua, Italy
| | - Davide Trez
- Department of Comparative Biomedicine and Food Science, University of Padua, Legnaro, Padua, Italy
| | - Raffaella De Maria
- Department of Veterinary Sciences, University of Turin, Grugliasco, Turin, Italy
| | - Donato Nitti
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | | | - Michelangelo Campanella
- Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, United Kingdom
- UCL Consortium for Mitochondrial Research, London, United Kingdom
| | - Marco Agostini
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
- Istituto di Ricerca Pediatrica – Città della Speranza, Padua, Italy
| | - Valentina Zappulli
- Department of Comparative Biomedicine and Food Science, University of Padua, Legnaro, Padua, Italy
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Perakis S, Auer M, Belic J, Heitzer E. Advances in Circulating Tumor DNA Analysis. Adv Clin Chem 2017; 80:73-153. [PMID: 28431643 DOI: 10.1016/bs.acc.2016.11.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The analysis of cell-free circulating tumor DNA (ctDNA) is a very promising tool and might revolutionize cancer care with respect to early detection, identification of minimal residual disease, assessment of treatment response, and monitoring tumor evolution. ctDNA analysis, often referred to as "liquid biopsy" offers what tissue biopsies cannot-a continuous monitoring of tumor-specific changes during the entire course of the disease. Owing to technological improvements, efforts for the establishment of preanalytical and analytical benchmark, and the inclusion of ctDNA analyses in clinical trial, an actual clinical implementation has come within easy reach. In this chapter, recent advances of the analysis of ctDNA are summarized starting from the discovery of cell-free DNA, to methodological approaches and the clinical applicability.
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Affiliation(s)
- Samantha Perakis
- Institute of Human Genetics, Medical University of Graz, Graz, Austria
| | - Martina Auer
- Institute of Human Genetics, Medical University of Graz, Graz, Austria
| | - Jelena Belic
- Institute of Human Genetics, Medical University of Graz, Graz, Austria
| | - Ellen Heitzer
- Institute of Human Genetics, Medical University of Graz, Graz, Austria.
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45
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Gao Z, Xue K, Zhang L, Wei M. Over-Expression of POU Class 1 Homeobox 1 Transcription Factor (Pit-1) Predicts Poor Prognosis for Breast Cancer Patients. Med Sci Monit 2016; 22:4121-4125. [PMID: 27798557 PMCID: PMC5094475 DOI: 10.12659/msm.896107] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Background The POU class 1 homeobox 1 transcription factor (POU1F1, also known as Pit-1) was reported to be associated with tumor progression and metastasis. The purpose of this study was to evaluate the prognostic value of Pit-1 in breast cancer patients. Material/Methods The relative expression levels of Pit-1 in breast cancer patients were detected by quantitative real-time PCR (qRT-PCR). Chi-square analysis was used to analyze the association between Pit-1 expression and clinical features. The Kaplan-Meier method was used to estimate the overall survival of the patients and Cox regression analysis was used to analyze the prognostic value of Pit-1. Results Increased expression of Pit-1 was detected in the tumor tissues compared with the normal tissues (1.086 vs. 0.541) and the abnormal expression was associated with tumor size, clinical stage, tumor grade, and lymph node metastasis (P<0.05). High expression level of Pit-1 was significantly associated with poor overall survival of the patients (P=0.001) and Cox regression analysis indicated that Pit-1 might be a prognostic factor for breast cancer prognosis (HR=1.955, 95% CI=1.295–3.035, P=0.003). Conclusions Pit-1 may be a potential prognostic biomarker for breast cancer patients and it is associated with tumor progression.
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Affiliation(s)
- Zhongcheng Gao
- Department of Thyroid and Breat Surgery, Linyi People's Hospital, Linyi, Shandong, China (mainland)
| | - Kecheng Xue
- Department of Thyroid and Breat Surgery, Linyi People's Hospital, Linyi, Shandong, China (mainland)
| | - Lianfang Zhang
- , North Courtyard Of Linyi People's Hospital, Linyi, Shandong, China (mainland)
| | - Meng Wei
- Department of Nursing, Linyi People's Hospital, Linyi, Shandong, China (mainland)
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46
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Huang A, Zhang X, Zhou SL, Cao Y, Huang XW, Fan J, Yang XR, Zhou J. Plasma Circulating Cell-free DNA Integrity as a Promising Biomarker for Diagnosis and Surveillance in Patients with Hepatocellular Carcinoma. J Cancer 2016; 7:1798-1803. [PMID: 27698918 PMCID: PMC5039362 DOI: 10.7150/jca.15618] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Accepted: 07/04/2016] [Indexed: 12/15/2022] Open
Abstract
The clinical significance of circulating cell-free DNA (cfDNA) integrity as diagnostic and surveillance biomarker in hepatocellular carcinoma (HCC) was investigated and compared to that of alpha fetoprotein (AFP). Liver cancer patients had lower cfDNA integrity than those with benign diseases (P = 0.0167) and healthy individuals (P = 0.0025). Patients with HCC and non-HCC liver cancers (P = 0.7356), and patients with benign diseases and healthy individuals (P = 0.9138) had comparable cfDNA integrity respectively. cfDNA integrity increased after hepatectomy in cancer patients (P = 0.0003). The AUCs for detecting HCC by cfDNA integrity and AFP were 0.705 (P = 0.005) and 0.605 (P = 0.156), respectively. We found cfDNA integrity decreased in HCC patients and has the potential as promising biomarker for HCC diagnosis and treatment surveillance.
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Affiliation(s)
- Ao Huang
- Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University
| | - Xin Zhang
- Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University
| | - Shao-Lai Zhou
- Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University
| | - Ya Cao
- Cancer Research Institute, Central South University
| | - Xiao-Wu Huang
- Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University
| | - Jia Fan
- Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University
- Institute of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Xin-Rong Yang
- Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University
| | - Jian Zhou
- Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University
- State Key Laboratory of Genetic Engineering Fudan University, Shanghai, 200433, China
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Utomo WK, Janmaat VT, Verhaar AP, Cros J, Lévy P, Ruszniewski P, den Berg MSVV, Jenster G, Bruno MJ, Braat H, Fuhler GM, Peppelenbosch MP. DNA integrity as biomarker in pancreatic cyst fluid. Am J Cancer Res 2016; 6:1837-1841. [PMID: 27648370 PMCID: PMC5004084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Accepted: 06/15/2016] [Indexed: 06/06/2023] Open
Abstract
Identification of pancreatic cysts with malignant potential is important to prevent pancreatic cancer development. Integrity of cell free DNA (cfDNA) has been described as tumor biomarker, but its potential for pancreatic cancer is unclear. While normal apoptotic cells release uniformly truncated DNA, malignant tissues release long fragments of cell free DNA (cfDNA). We measured 247 base pair (bp) and 115 bp DNA fragments of ALU repeats by qPCR in serum from healthy controls and pancreatic cancer patients, and in cyst fluid from pancreatic cyst patients. No differences in total cfDNA (ALU115) and cfDNA integrity (ALU247/115) were observed between sera from healthy controls (n=19) and pancreatic cancer patients (n=19). Although elevated as compared to serum, but no differences in cfDNA were found in cyst fluid from high risk (n=10) and low risk (n=20) cyst patients. We conclude that cfDNA integrity is not a useful marker to identify (pre)malignant pancreatic lesions.
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Affiliation(s)
- Wesley K Utomo
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical CenterRotterdam, The Netherlands
| | - Vincent T Janmaat
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical CenterRotterdam, The Netherlands
| | - Auke P Verhaar
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical CenterRotterdam, The Netherlands
| | - Jérôme Cros
- Department de Pathology, Hôpital Beaujon, INSERM U1149, Université Paris DiderotClichy, France
| | - Philippe Lévy
- Service de Pancréatologie-Gastroentérologie, Pôle des Maladies de l’Appareil Digestif Université Denis Diderot-Paris VII Hôpital BeaujonClichy Cedex, France
| | - Philippe Ruszniewski
- Service de Pancréatologie-Gastroentérologie, Pôle des Maladies de l’Appareil Digestif Université Denis Diderot-Paris VII Hôpital BeaujonClichy Cedex, France
| | | | - Guido Jenster
- Department of Urology, Erasmus MC University Medical CenterRotterdam, The Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical CenterRotterdam, The Netherlands
| | - Henri Braat
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical CenterRotterdam, The Netherlands
| | - Gwenny M Fuhler
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical CenterRotterdam, The Netherlands
| | - Maikel P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical CenterRotterdam, The Netherlands
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Gui Z, Wang Q, Li J, Zhu M, Yu L, Xun T, Yan F, Ju H. Direct detection of circulating free DNA extracted from serum samples of breast cancer using locked nucleic acid molecular beacon. Talanta 2016; 154:520-5. [PMID: 27154709 DOI: 10.1016/j.talanta.2016.04.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2015] [Revised: 03/25/2016] [Accepted: 04/03/2016] [Indexed: 12/24/2022]
Abstract
As an emerging noninvasive blood biomarker, circulating free DNA (cfDNA) can be utilized to assess diagnosis, progression and evaluate prognosis of cancer. However, cfDNAs are not "naked", they can be part of complexes, or are bound to the surface of the cells via proteins, which make the detection more challenging. Here, a simple method for the detection of Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) DNA exacted from serum of breast cancer (BC) has been developed using a novel locked nucleic acid molecular beacon (LNA-MB). In order to enhance the stability and detection efficiency of the probe in biofluids, we design a shared-stem molecular beacon containing a 27-mer loop and a 4-mer stem with DNA/LNA alternating bases. The fluorescence is released in the presence of target. The detection procedure is simple and can be completed within 1h. This method shows a sensitive response to UHRF1 DNA with a dynamic range of 3 orders of magnitude. The limit of detection is 11nM (S/N=3) with excellent selectivity. It can discriminate UHRF1 DNA from three-base mismatched DNA with a high specificity. More importantly, this method can distinguish the expression of serum UHRF1 DNA among 5 breast cancer patients and 5 healthy controls. The mentioned superiority may suggest that this assay can be served as a promising noninvasive detection tool for early BC diagnosis and monitoring.
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Affiliation(s)
- Zhen Gui
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital, Nanjing 210009, PR China
| | - Quanbo Wang
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, PR China
| | - Jinchang Li
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital, Nanjing 210009, PR China
| | - Mingchen Zhu
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital, Nanjing 210009, PR China
| | - Lili Yu
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital, Nanjing 210009, PR China
| | - Tang Xun
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital, Nanjing 210009, PR China
| | - Feng Yan
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital, Nanjing 210009, PR China.
| | - Huangxian Ju
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, PR China.
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Canzoniero JV, Park BH. Use of cell free DNA in breast oncology. Biochim Biophys Acta Rev Cancer 2016; 1865:266-74. [PMID: 27012505 DOI: 10.1016/j.bbcan.2016.03.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2016] [Revised: 03/18/2016] [Accepted: 03/19/2016] [Indexed: 12/24/2022]
Abstract
Cell free DNA (cfDNA) are short fragments of nucleic acids present in circulation outside of cells. In patients with cancer, some portion of cfDNA is derived from tumor cells, termed circulating tumor DNA (ctDNA), and contains the same mutations and genetic changes as the cancer. The development of new, more effective methods to detect these changes has led to increased interest in developing ctDNA as a biomarker for cancer. Here we will review current literature on the use of ctDNA, with an emphasis on breast cancer, for cancer detection, prognosis, monitoring response to therapy, and tracking the rise of new mutant subclones.
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Affiliation(s)
- Jenna VanLiere Canzoniero
- Division of General Internal Medicine, Johns Hopkins, 600 N Wolfe St, Nelson 207, Baltimore, MD 21287, USA.
| | - Ben Ho Park
- The Sidney Kimmel Comprehensive Cancer Institute at Johns Hopkins, 1650 Orleans Street, CRBI, Baltimore, MD 21287, USA.
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50
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El Messaoudi S, Mouliere F, Du Manoir S, Bascoul-Mollevi C, Gillet B, Nouaille M, Fiess C, Crapez E, Bibeau F, Theillet C, Mazard T, Pezet D, Mathonnet M, Ychou M, Thierry AR. Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care. Clin Cancer Res 2016; 22:3067-77. [DOI: 10.1158/1078-0432.ccr-15-0297] [Citation(s) in RCA: 114] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Accepted: 01/03/2016] [Indexed: 02/07/2023]
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