|
1
|
Song J, Ye X, Xiao H. Liquid biopsy entering clinical practice: Past discoveries, current insights, and future innovations. Crit Rev Oncol Hematol 2025; 207:104613. [PMID: 39756526 DOI: 10.1016/j.critrevonc.2025.104613] [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: 11/20/2024] [Revised: 12/22/2024] [Accepted: 01/02/2025] [Indexed: 01/07/2025] Open
Abstract
In recent years, liquid biopsy has gained prominence as an emerging biomarker in cancer research, providing critical insights into tumor biology and metastasis. Technological advancements have enabled its integration into clinical practice, with ongoing trials demonstrating encouraging outcomes. Key applications of liquid biopsy include early cancer detection, cancer staging, prognosis evaluation, and real-time monitoring of tumor progression to optimize treatment decisions. In this review, we present a comprehensive conceptual framework for liquid biopsy, discuss the challenges in its research and clinical application, and highlight its significant potential in identifying therapeutic targets and resistance mechanisms across various cancer types. Furthermore, we explore the emerging role of liquid biopsy-based multicancer screening, which has shown promising advancements. Looking ahead, standardization, multi-omics coanalysis, and the advancement of precision medicine and personalized treatments are expected to drive the future development and integration of liquid biopsy into routine clinical workflows, enhancing cancer diagnosis and treatment management.
Collapse
Affiliation(s)
- Jinghan Song
- Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiong Ye
- School of Clinical Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Hui Xiao
- Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| |
Collapse
|
|
2
|
Artner T, Sharma S, Lang IM. Nucleic acid liquid biopsies in cardiovascular disease: Cell-free DNA liquid biopsies in cardiovascular disease. Atherosclerosis 2024; 398:118583. [PMID: 39353793 DOI: 10.1016/j.atherosclerosis.2024.118583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 08/15/2024] [Accepted: 08/29/2024] [Indexed: 10/04/2024]
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide, and despite treatment efforts, cardiovascular function cannot always be restored, and progression of disease be prevented. Critical insights are oftentimes based on tissue samples. Current knowledge of tissue pathology typically relies on invasive biopsies or postmortem samples. Liquid biopsies, which assess circulating mediators to deduce the histology and pathology of distant tissues, have been advancing rapidly in cancer research and offer a promising approach to be translated to the understanding and treatment of CVD. The widely understood elevations in cell-free DNA during acute and chronic cardiovascular conditions, associate with disease, severity, and offer prognostic value. The role of neutrophil extracellular traps (NETs) and circulating nucleases in thrombosis provide a solid rationale for liquid biopsies in CVD. cfDNA originates from various tissue types and cellular sources, including mitochondria and nuclei, and can be used to trace cell and tissue type lineage, as well as to gain insight into the activation status of cells. This article discusses the origin, structure, and potential utility of cfDNA, offering a deeper and less invasive approach for the understanding of the complexities of CVD.
Collapse
Affiliation(s)
- Tyler Artner
- Department of Internal Medicine II, Cardiology, Medical University of Vienna, Austria.
| | - Smriti Sharma
- Department of Internal Medicine II, Cardiology, Medical University of Vienna, Austria
| | - Irene M Lang
- Department of Internal Medicine II, Cardiology, Medical University of Vienna, Austria.
| |
Collapse
|
|
3
|
Mondal D, Shinde S, Sinha V, Dixit V, Paul S, Gupta RK, Thakur S, Vishvakarma NK, Shukla D. Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers. Front Mol Biosci 2024; 11:1385238. [PMID: 38770216 PMCID: PMC11103528 DOI: 10.3389/fmolb.2024.1385238] [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: 02/12/2024] [Accepted: 04/08/2024] [Indexed: 05/22/2024] Open
Abstract
Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers.
Collapse
Affiliation(s)
- Deepankar Mondal
- Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India
| | - Sapnita Shinde
- Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India
| | - Vibha Sinha
- Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India
| | - Vineeta Dixit
- Department of Botany, Sri Sadguru Jagjit Singh Namdhari College, Garhwa, Jharkhand, India
| | - Souvik Paul
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
| | - Rakesh Kumar Gupta
- Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
| | | | | | - Dhananjay Shukla
- Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India
| |
Collapse
|
|
4
|
Abstract
The cumulative pool of cell-free DNA (cfDNA) molecules within bodily fluids represents a highly dense and multidimensional information repository. This "biological mirror" provides real-time insights into the composition, function, and dynamics of the diverse genomes within the body, enabling significant advancements in personalized molecular medicine. However, effective use of this information necessitates meticulous classification of distinct cfDNA subtypes with exceptional precision. While cfDNA molecules originating from different sources exhibit numerous genetic, epigenetic, and physico-chemical variations, they also share common features that complicate analyses. Considerable progress has been achieved in mapping the landscape of cfDNA features, their clinical correlations, and optimizing extraction procedures, analytical approaches, bioinformatics pipelines, and machine learning algorithms. Nevertheless, preanalytical workflows, despite their profound impact on cfDNA measurements, have not progressed at a corresponding pace. In this perspective article, we emphasize the pivotal role of robust preanalytical procedures in the development and clinical integration of cfDNA assays, highlighting persistent obstacles and emerging challenges.
Collapse
Affiliation(s)
- Abel J Bronkhorst
- Munich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University Munich, Munich, Germany
| | - Stefan Holdenrieder
- Munich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University Munich, Munich, Germany
| |
Collapse
|
|
5
|
Pecere S, Ciuffini C, Chiappetta MF, Petruzziello L, Papparella LG, Spada C, Gasbarrini A, Barbaro F. Increasing the accuracy of colorectal cancer screening. Expert Rev Anticancer Ther 2023; 23:583-591. [PMID: 37099725 DOI: 10.1080/14737140.2023.2207828] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
INTRODUCTION Colorectal cancer (CRC) is a major health issue, being responsible for nearly 10% of all cancer-related deaths. Since CRC is often an asymptomatic or paucisymptomatic disease until it reaches advanced stages, screening is crucial for the diagnosis of preneoplastic lesions or early CRC. AREAS COVERED The aim of this review is to summarize the literature evidence on currently available CRC screening tools, with their pros and cons, focusing on the level of accuracy reached by each test over time. We also provide an overview of novel technologies and scientific advances that are currently being investigated and that in the future may represent real game-changers in the field of CRC screening. EXPERT OPINION We suggest that best screening modalities are annual or biennial FIT and colonoscopy every 10 years. We believe that the introduction of artificial intelligence (AI)-tools in the CRC screening field could lead to a significant improvement of the screening efficacy in reducing CRC incidence and mortality in the future. More resources should be put into implementing CRC programmes and support research project to further increase accuracy of CRC screening tests and strategies.
Collapse
Affiliation(s)
- Silvia Pecere
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Cristina Ciuffini
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Michele Francesco Chiappetta
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Lucio Petruzziello
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Luigi Giovanni Papparella
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Cristiano Spada
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Antonio Gasbarrini
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Federico Barbaro
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| |
Collapse
|
|
6
|
Yao T, Sun Q, Xiong K, Su Y, Zhao Q, Zhang C, Zhang L, Li X, Fang H. Optimization of screening strategies for colorectal cancer based on fecal DNA and occult blood testing. Eur J Public Health 2023; 33:336-341. [PMID: 36905607 PMCID: PMC10066493 DOI: 10.1093/eurpub/ckad032] [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] [Indexed: 03/12/2023] Open
Abstract
BACKGROUND Fecal DNA and occult blood testing have been gradually developed for colorectal cancer (CRC) screening. Comparison of different testing strategies for these methods in CRC screening is in urgent need. This study aims to examine the efficacy of different testing strategies including multi-target fecal DNA testing, qualitative and quantitative fecal immunoassay tests (FITs). METHODS Fecal samples were collected from patients diagnosed by colonoscopy. Tests using fecal DNA, quantitative FIT or qualitative FIT were performed on same fecal samples. Efficiency of different testing strategies within different populations was investigated. RESULTS For high-risk populations (CRC and advanced adenoma), the positive rate of the three methods alone was 74.3-80%; the positive predictive values (PPVs) ranged from 37.3% to 77.8%, and the negative predictive values (NPVs) ranged from 86.3% to 92.2%. For combined testing strategies, the positive rate was 71.4-88.6%, PPVs ranged from 38.3% to 86.2%, and NPVs ranged from 89.6% to 92.9%. Parallel fecal multi-target DNA test and quantitative FIT appears to be superior when using a combined testing strategy. For the normal population, no significant difference was identified in efficacy between these methods when used alone and in combination. CONCLUSIONS Single testing strategy among the three methods is more suitable for the general population screening, and the combined testing strategy is more suitable for high-risk populations screening. The use of different combination strategies may have superiority in CRC high-risk population screening, but cannot conclude significant differences which may be attributed to the small sample size, large samples controlled trials are needed.
Collapse
Affiliation(s)
- Tingting Yao
- Department of Gastroenterology, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
- Center of Gut Microbiota, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Qin Sun
- Department of Gastroenterology, The Second Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, China
| | - Kangwei Xiong
- Department of Gastroenterology, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
- Center of Gut Microbiota, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Yuan Su
- Department of Gastroenterology, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
- Center of Gut Microbiota, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Qian Zhao
- Department of Gastroenterology, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
- Center of Gut Microbiota, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Chenhong Zhang
- Department of Gastroenterology, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
- Center of Gut Microbiota, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Lijiu Zhang
- Department of Gastroenterology, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
- Center of Gut Microbiota, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Xuejun Li
- Department of Gastroenterology, The Second Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, China
| | - Haiming Fang
- Department of Gastroenterology, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
- Center of Gut Microbiota, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
| |
Collapse
|
|
7
|
Ko B, Hanna M, Yu M, Grady WM. Epigenetic Alterations in Colorectal Cancer. EPIGENETICS AND HUMAN HEALTH 2023:331-361. [DOI: 10.1007/978-3-031-42365-9_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
8
|
Doleschal B, Petzer A, Rumpold H. Current concepts of anti-EGFR targeting in metastatic colorectal cancer. Front Oncol 2022; 12:1048166. [PMID: 36465407 PMCID: PMC9714621 DOI: 10.3389/fonc.2022.1048166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 10/26/2022] [Indexed: 11/07/2023] Open
Abstract
Anti-EGFR targeting is one of the key strategies in the treatment of metastatic colorectal cancer (mCRC). For almost two decades oncologists have struggled to implement EGFR antibodies in the mCRC continuum of care. Both sidedness and RAS mutational status rank high among the predictive factors for the clinical efficacy of EGFR inhibitors. A prospective phase III trial has recently confirmed that anti-EGFR targeting confers an overall survival benefit only in left sided RAS-wildtype tumors when given in first line. It is a matter of discussion if more clinical benefit can be reached by considering putative primary resistance mechanisms (e.g., HER2, BRAF, PIK3CA, etc.) at this early stage of treatment. The value of this procedure in daily routine clinical utility has not yet been clearly delineated. Re-exposure to EGFR antibodies becomes increasingly crucial in the disease journey of mCRC. Yet re- induction or re-challenge strategies have been problematic as they relied on mathematical models that described the timely decay of EGFR antibody resistant clones. The advent of liquid biopsy and the implementation of more accurate next-generation sequencing (NGS) based high throughput methods allows for tracing of EGFR resistant clones in real time. These displays the spatiotemporal heterogeneity of metastatic disease compared to the former standard radiographic assessment and re-biopsy. These techniques may move EGFR inhibition in mCRC into the area of precision medicine in order to apply EGFR antibodies with the increase or decrease of EGFR resistant clones. This review critically discusses established concepts of tackling the EGFR pathway in mCRC and provides insight into the growing field of liquid biopsy guided personalized approaches of EGFR inhibition in mCRC.
Collapse
Affiliation(s)
- Bernhard Doleschal
- Department of Internal Medicine I for Hematology With Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz, Linz, Austria
| | - Andreas Petzer
- Department of Internal Medicine I for Hematology With Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz, Linz, Austria
| | - Holger Rumpold
- Gastrointestinal Cancer Center, Ordensklinikum Linz, Linz, Austria
- Johannes Kepler University Linz, Medical Faculty, Linz, Austria
| |
Collapse
|
|
9
|
Bronkhorst AJ, Ungerer V, Oberhofer A, Gabriel S, Polatoglou E, Randeu H, Uhlig C, Pfister H, Mayer Z, Holdenrieder S. New Perspectives on the Importance of Cell-Free DNA Biology. Diagnostics (Basel) 2022; 12:2147. [PMID: 36140548 PMCID: PMC9497998 DOI: 10.3390/diagnostics12092147] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 08/24/2022] [Accepted: 08/31/2022] [Indexed: 11/28/2022] Open
Abstract
Body fluids are constantly replenished with a population of genetically diverse cell-free DNA (cfDNA) fragments, representing a vast reservoir of information reflecting real-time changes in the host and metagenome. As many body fluids can be collected non-invasively in a one-off and serial fashion, this reservoir can be tapped to develop assays for the diagnosis, prognosis, and monitoring of wide-ranging pathologies, such as solid tumors, fetal genetic abnormalities, rejected organ transplants, infections, and potentially many others. The translation of cfDNA research into useful clinical tests is gaining momentum, with recent progress being driven by rapidly evolving preanalytical and analytical procedures, integrated bioinformatics, and machine learning algorithms. Yet, despite these spectacular advances, cfDNA remains a very challenging analyte due to its immense heterogeneity and fluctuation in vivo. It is increasingly recognized that high-fidelity reconstruction of the information stored in cfDNA, and in turn the development of tests that are fit for clinical roll-out, requires a much deeper understanding of both the physico-chemical features of cfDNA and the biological, physiological, lifestyle, and environmental factors that modulate it. This is a daunting task, but with significant upsides. In this review we showed how expanded knowledge on cfDNA biology and faithful reverse-engineering of cfDNA samples promises to (i) augment the sensitivity and specificity of existing cfDNA assays; (ii) expand the repertoire of disease-specific cfDNA markers, thereby leading to the development of increasingly powerful assays; (iii) reshape personal molecular medicine; and (iv) have an unprecedented impact on genetics research.
Collapse
Affiliation(s)
- Abel J. Bronkhorst
- Munich Biomarker Research Center, Institute for Laboratory Medicine, German Heart Centre, Technical University Munich, Lazarettstraße 36, D-80636 Munich, Germany
| | | | | | | | | | | | | | | | | | - Stefan Holdenrieder
- Munich Biomarker Research Center, Institute for Laboratory Medicine, German Heart Centre, Technical University Munich, Lazarettstraße 36, D-80636 Munich, Germany
| |
Collapse
|
|
10
|
Mauri G, Vitiello PP, Sogari A, Crisafulli G, Sartore-Bianchi A, Marsoni S, Siena S, Bardelli A. Liquid biopsies to monitor and direct cancer treatment in colorectal cancer. Br J Cancer 2022; 127:394-407. [PMID: 35264786 PMCID: PMC9346106 DOI: 10.1038/s41416-022-01769-8] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 02/02/2022] [Accepted: 02/17/2022] [Indexed: 12/15/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide. Despite recent improvements in treatment and prevention, most of the current therapeutic options are weighted by side effects impacting patients' quality of life. Better patient selection towards systemic treatments represents an unmet clinical need. The recent multidisciplinary and molecular advancements in the treatment of CRC patients demand the identification of efficient biomarkers allowing to personalise patient care. Currently, core tumour biopsy specimens represent the gold-standard biological tissue to identify such biomarkers. However, technical feasibility, tumour heterogeneity and cancer evolution are major limitations of this single-snapshot approach. Genotyping circulating tumour DNA (ctDNA) has been addressed as potentially overcoming such limitations. Indeed, ctDNA has been retrospectively demonstrated capable of identifying minimal residual disease post-surgery and post-adjuvant treatment, as well as spotting druggable molecular alterations for tailoring treatments in metastatic disease. In this review, we summarise the available evidence on ctDNA applicability in CRC. Then, we review ongoing clinical trials assessing how liquid biopsy can be used interventionally to guide therapeutic choice in localised, locally advanced and metastatic CRC. Finally, we discuss how its widespread could transform CRC patients' management, dissecting its limitations while suggesting improvement strategies.
Collapse
Affiliation(s)
- Gianluca Mauri
- IFOM-FIRC Institute of Molecular Oncology, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Pietro Paolo Vitiello
- Candiolo Cancer Institute, FPO-IRCCS, 10060, Candiolo, TO, Italy
- Department of Oncology, University of Torino, 10060, Candiolo, TO, Italy
| | - Alberto Sogari
- Candiolo Cancer Institute, FPO-IRCCS, 10060, Candiolo, TO, Italy
- Department of Oncology, University of Torino, 10060, Candiolo, TO, Italy
| | - Giovanni Crisafulli
- Candiolo Cancer Institute, FPO-IRCCS, 10060, Candiolo, TO, Italy
- Department of Oncology, University of Torino, 10060, Candiolo, TO, Italy
| | - Andrea Sartore-Bianchi
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | | | - Salvatore Siena
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | - Alberto Bardelli
- Candiolo Cancer Institute, FPO-IRCCS, 10060, Candiolo, TO, Italy.
- Department of Oncology, University of Torino, 10060, Candiolo, TO, Italy.
| |
Collapse
|
|
11
|
He J, Xi N, Han Z, Luo W, Shen J, Wang S, Li J, Guo Z, Cheng H. The Role of Liquid Biopsy Analytes in Diagnosis, Treatment and Prognosis of Colorectal Cancer. Front Endocrinol (Lausanne) 2022; 13:875442. [PMID: 35846270 PMCID: PMC9279561 DOI: 10.3389/fendo.2022.875442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 04/26/2022] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract worldwide and is a serious threat to human life and health. CRC occurs and develops in a multi-step, multi-stage, and multi-gene process, in which abnormal gene expression plays an important role. CRC is currently diagnosed via endoscopy combined with tissue biopsy. Compared with tissue biopsy, liquid biopsy technology has received increasingly more attention and applications in the field of molecular detection due to its non-invasive, safe, comprehensive, and real-time dynamic nature. This review article discusses the application and limitations of current liquid biopsy analytes in the diagnosis, treatment, and prognosis of CRC, as well as directions for their future development.
Collapse
Affiliation(s)
- JinHua He
- Central Laboratory of Panyu Central Hospital, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - NaiTe Xi
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - ZePing Han
- Central Laboratory of Panyu Central Hospital, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - WenFeng Luo
- Central Laboratory of Panyu Central Hospital, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - Jian Shen
- Central Laboratory of Panyu Central Hospital, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - ShengBo Wang
- Department of Gastroenterology, Central Hospital of Panyu District, Guangzhou, China
| | - JianHao Li
- Institute of Cardiovascular Medicine, Central Hospital of Panyu District, Guangzhou, China
| | - ZhongHui Guo
- Central Laboratory of Panyu Central Hospital, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - HanWei Cheng
- Central Laboratory of Panyu Central Hospital, Guangzhou Panyu Central Hospital, Guangzhou, China
| |
Collapse
|
|
12
|
Evaluation of combined detection of multigene mutation and SDC2/SFRP2 methylation in stool specimens for colorectal cancer early diagnosis. Int J Colorectal Dis 2022; 37:1231-1238. [PMID: 35499710 DOI: 10.1007/s00384-022-04170-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/22/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE Molecular diagnostics of colorectal cancer (CRC) can be used as an auxiliary approach for patients recommended for colonoscopy, providing more CRC supplemental diagnosis options. This study investigated whether combined detection of KRAS/BRAF/APC mutation and SDC2/SFRP2 methylation can serve as auxiliary diagnostics in clinical management. METHODS KRAS/BRAF/APC mutation and SDC2/SFRP2 methylation in stool samples from healthy donors, patients with CRC, advanced adenoma (AA), non-advanced adenoma (NAA), or other gastroenterological diseases were evaluated using quantitative PCR (qPCR) or methylation-specific quantitative PCR (MSP). Test accuracy was determined by evaluating the tests' sensitivity, specificity, positive/negative predictive value (PPV/NPV), or positive/negative likelihood ratio (PLR/NLR). RESULTS The combined fecal KRAS/BRAF/APC mutation and SFRP2/SDC2 methylation detection test achieved a sensitivity of 88.57% with a PPV of 93.64% and a PLR of 7.10 for CRC patients. In comparison, the corresponding parameters for multigene mutation were 46.67%, 92.59%, and 36.26 and 83.81%, 93.94%, and 7.47, for DNA methylation, separately. The sensitivity of the combined test, gene mutation test, and DNA methylation test approach was 75%, 28.26%, and 72.83%. Furthermore, the specificity of this approach in the NAA group was 79.49%. Meanwhile, the overall diagnostic specificity for the combined test in NAA, healthy control, and interference groups was 88.42%. In addition, the sensitivity of the combined detection method increased with the disease stage in CRC patients and elevated along with the lesion size (≥ 1 cm) in AA patients. CONCLUSION Combined detection of fecal KRAS/BRAF/APC mutation and SFRP2/SDC2 methylation has potential application value for the auxiliary diagnosis of CRC and AA.
Collapse
|
|
13
|
Hua H, Meydan C, Afshin EE, Lili LN, D’Adamo CR, Rickard N, Dudley JT, Price ND, Zhang B, Mason CE. A Wipe-Based Stool Collection and Preservation Kit for Microbiome Community Profiling. Front Immunol 2022; 13:889702. [PMID: 35711426 PMCID: PMC9196042 DOI: 10.3389/fimmu.2022.889702] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/03/2022] [Indexed: 11/13/2022] Open
Abstract
While a range of methods for stool collection exist, many require complicated, self-directed protocols and stool transfer. In this study, we introduce and validate a novel, wipe-based approach to fecal sample collection and stabilization for metagenomics analysis. A total of 72 samples were collected across four different preservation types: freezing at -20°C, room temperature storage, a commercial DNA preservation kit, and a dissolvable wipe used with DESS (dimethyl sulfoxide, ethylenediaminetetraacetic acid, sodium chloride) solution. These samples were sequenced and analyzed for taxonomic abundance metrics, bacterial metabolic pathway classification, and diversity analysis. Overall, the DESS wipe results validated the use of a wipe-based capture method to collect stool samples for microbiome analysis, showing an R2 of 0.96 for species across all kingdoms, as well as exhibiting a maintenance of Shannon diversity (3.1-3.3) and species richness (151-159) compared to frozen samples. Moreover, DESS showed comparable performance to the commercially available preservation kit (R2 of 0.98), and samples consistently clustered by subject across each method. These data support that the DESS wipe method can be used for stable, room temperature collection and transport of human stool specimens.
Collapse
Affiliation(s)
- Hui Hua
- Thorne HealthTech, New York, NY, United States
| | - Cem Meydan
- Thorne HealthTech, New York, NY, United States
| | | | | | - Christopher R. D’Adamo
- Department of Family and Community Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | | | | | - Nathan D. Price
- Thorne HealthTech, New York, NY, United States
- Institute for Systems Biology, Seattle, WA, United States
| | - Bodi Zhang
- Thorne HealthTech, New York, NY, United States
| | - Christopher E. Mason
- Thorne HealthTech, New York, NY, United States
- The WorldQuant Initiative for Quantitative Prediction, New York, NY, United States
| |
Collapse
|
|
14
|
Symer M, Connolly J, Yeo H. Management of the Malignant Colorectal Polyp. Curr Probl Surg 2022; 59:101124. [DOI: 10.1016/j.cpsurg.2022.101124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
|
|
15
|
Biomarker-Based Evaluation of Treatment Response and Surveillance of HPV-Associated Squamous Cell Carcinoma. CURRENT OTORHINOLARYNGOLOGY REPORTS 2022. [DOI: 10.1007/s40136-021-00386-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
|
|
16
|
PCR-Based Analytical Methods for Quantification and Quality Control of Recombinant Adeno-Associated Viral Vector Preparations. Pharmaceuticals (Basel) 2021; 15:ph15010023. [PMID: 35056080 PMCID: PMC8779925 DOI: 10.3390/ph15010023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 12/17/2021] [Accepted: 12/22/2021] [Indexed: 11/17/2022] Open
Abstract
Recombinant adeno-associated viral vectors (rAAV) represent a gene therapy tool of ever-increasing importance. Their utilization as a delivery vehicle for gene replacement, silencing and editing, among other purposes, demonstrate considerable versatility. Emerging vector utilization in various experimental, preclinical and clinical applications establishes the necessity of producing and characterizing a wide variety of rAAV preparations. Critically important characteristics concerning quality control are rAAV titer quantification and the detection of impurities. Differences in rAAV constructs necessitate the development of highly standardized quantification assays to make direct comparisons of different preparations in terms of assembly or purification efficiency, as well as experimental or therapeutic dosages. The development of universal methods for impurities quantification is rather complicated, since variable production platforms are utilized for rAAV assembly. However, general agreements also should be achieved to address this issue. The majority of methods for rAAV quantification and quality control are based on PCR techniques. Despite the progress made, increasing evidence concerning high variability in titration assays indicates poor standardization of the methods undertaken to date. This review summarizes successes in the field of rAAV quality control and emphasizes ongoing challenges in PCR applications for rAAV characterization. General considerations regarding possible solutions are also provided.
Collapse
|
|
17
|
He S, Zhou C, Peng H, Lin M. Recent advances in fecal gene detection for colorectal cancer diagnosis. Biomark Med 2021; 15:1299-1308. [PMID: 34544268 DOI: 10.2217/bmm-2021-0269] [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
There has been a gradual increase in the incidence of colorectal cancer (CRC) in recent years. Most patients lack obvious early symptoms, but are commonly in mid and advanced stages when the symptoms become evident, with rather high mortalities. Early diagnosis, treatment and recurrence monitoring are crucial to improving the recovery rate of CRC. Studies have shown that tumor-related genes can be detected in the feces of CRC patients. Owing to non-invasiveness, convenient sampling and continuous dynamic monitoring, fecal gene detection may be applicable to CRC screening, diagnosis, prognostic assessment and recurrence monitoring. Herein, we review the research advances in fecal gene detection for CRC diagnosis.
Collapse
Affiliation(s)
- Siyu He
- Clinical Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou, 225300, Jiangsu, China
| | - Chenglin Zhou
- Clinical Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou, 225300, Jiangsu, China
| | - Hailin Peng
- Clinical Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou, 225300, Jiangsu, China
| | - Mei Lin
- Clinical Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou, 225300, Jiangsu, China
| |
Collapse
|
|
18
|
Abstract
Metastases are the most common intracranial tumors in adults. Lung cancer, melanoma, renal cell carcinoma, and breast cancer are the most common primary tumors that metastasize to the brain. Improved detection of small metastases by MRI, and improved systemic therapy for primary tumors, resulted in increased incidence of brain metastasis. Advances in neuroanesthesia and neurosurgery have significantly improved the safety of surgical resection of brain metastases. Surgical approach and active management have become applicable for many patients. Subsequently, brain metastases diagnosis no longer equals palliative treatment. Moreover, the demand for diagnosing brain masses has increased with its associated challenges.
Collapse
Affiliation(s)
- Saber Tadros
- Laboratory of Pathology, National Cancer Institute, 10 Center Drive, Building 10, Room 3N248, Bethesda, MD 20814, USA.
| | - Abhik Ray-Chaudhury
- Surgical Neurology Branch, National Cancer Institute, 10 Center Drive, Building 10, Room 3D-03, MSC1414, Bethesda, MD 20892-3704, USA
| |
Collapse
|
|
19
|
Mazouji O, Ouhajjou A, Incitti R, Mansour H. Updates on Clinical Use of Liquid Biopsy in Colorectal Cancer Screening, Diagnosis, Follow-Up, and Treatment Guidance. Front Cell Dev Biol 2021; 9:660924. [PMID: 34150757 PMCID: PMC8213391 DOI: 10.3389/fcell.2021.660924] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 03/30/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide, being the third most diagnosed in the world and the second deadliest. Solid biopsy provides an essential guide for the clinical management of patients with colorectal cancer; however, this method presents several limitations, in particular invasiveness, and cannot be used repeatedly. Recently, clinical research directed toward the use of liquid biopsy, as an alternative tool to solid biopsy, showed significant promise in several CRC clinical applications, as (1) detect CRC patients at early stage, (2) make treatment decision, (3) monitor treatment response, (4) predict relapses and metastases, (5) unravel tumor heterogeneity, and (6) detect minimal residual disease. The purpose of this short review is to describe the concept, the characteristics, the genetic components, and the technologies used in liquid biopsy in the context of the management of colorectal cancer, and finally we reviewed gene alterations, recently described in the literature, as promising potential biomarkers that may be specifically used in liquid biopsy tests.
Collapse
Affiliation(s)
- Omayma Mazouji
- GES-LCM2E, FPN, Mohamed First University, Oujda, Morocco
| | | | - Roberto Incitti
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
| | - Hicham Mansour
- GES-LCM2E, FPN, Mohamed First University, Oujda, Morocco
| |
Collapse
|
|
20
|
Green EA, Li R, Albiges L, Choueiri TK, Freedman M, Pal S, Dyrskjøt L, Kamat AM. Clinical Utility of Cell-free and Circulating Tumor DNA in Kidney and Bladder Cancer: A Critical Review of Current Literature. Eur Urol Oncol 2021; 4:893-903. [DOI: 10.1016/j.euo.2021.04.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 03/28/2021] [Accepted: 04/15/2021] [Indexed: 12/14/2022]
|
|
21
|
Gachabayov M, Lebovics E, Rojas A, Felsenreich DM, Latifi R, Bergamaschi R. Performance evaluation of stool DNA methylation tests in colorectal cancer screening: a systematic review and meta-analysis. Colorectal Dis 2021; 23:1030-1042. [PMID: 33410272 DOI: 10.1111/codi.15521] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 12/30/2020] [Accepted: 12/30/2020] [Indexed: 12/16/2022]
Abstract
AIM There is not sufficient evidence about whether stool DNA methylation tests allow prioritizing patients to colonoscopy. Due to the COVID-19 pandemic, there will be a wait-list for rescheduling colonoscopies once the mitigation is lifted. The aim of this meta-analysis was to evaluate the accuracy of stool DNA methylation tests in detecting colorectal cancer. METHODS The PubMed, Cochrane Library and MEDLINE via Ovid were searched. Studies reporting the accuracy (Sackett phase 2 or 3) of stool DNA methylation tests to detect sporadic colorectal cancer were included. The DerSimonian-Laird method with random-effects model was utilized for meta-analysis. RESULTS Forty-six studies totaling 16 149 patients were included in the meta-analysis. The pooled sensitivity and specificity of all single genes and combinations was 62.7% (57.7%, 67.4%) and 91% (89.5%, 92.2%), respectively. Combinations of genes provided higher sensitivity compared to single genes (80.8% [75.1%, 85.4%] vs. 57.8% [52.3%, 63.1%]) with no significant decrease in specificity (87.8% [84.1%, 90.7%] vs. 92.1% [90.4%, 93.5%]). The most accurate single gene was found to be SDC2 with a sensitivity of 83.1% (72.6%, 90.2%) and a specificity of 91.2% (88.6%, 93.2%). CONCLUSIONS Stool DNA methylation tests have high specificity (92%) with relatively lower sensitivity (81%). Combining genes increases sensitivity compared to single gene tests. The single most accurate gene is SDC2, which should be considered for further research.
Collapse
Affiliation(s)
- Mahir Gachabayov
- Section of Colorectal Surgery, Department of Surgery, Westchester Medical Center, New York Medical College, Valhalla, NY, USA
| | - Edward Lebovics
- Section of Gastroenterology, Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY, USA
| | - Aram Rojas
- Section of Colorectal Surgery, Department of Surgery, Westchester Medical Center, New York Medical College, Valhalla, NY, USA
| | - Daniel M Felsenreich
- Section of Colorectal Surgery, Department of Surgery, Westchester Medical Center, New York Medical College, Valhalla, NY, USA
| | - Rifat Latifi
- Section of Colorectal Surgery, Department of Surgery, Westchester Medical Center, New York Medical College, Valhalla, NY, USA
| | - Roberto Bergamaschi
- Section of Colorectal Surgery, Department of Surgery, Westchester Medical Center, New York Medical College, Valhalla, NY, USA
| |
Collapse
|
|
22
|
Grady WM. Epigenetic alterations in the gastrointestinal tract: Current and emerging use for biomarkers of cancer. Adv Cancer Res 2021; 151:425-468. [PMID: 34148620 DOI: 10.1016/bs.acr.2021.02.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Colorectal cancer is a leading cause of cancer related deaths worldwide. One of the hallmarks of cancer and a fundamental trait of virtually all gastrointestinal cancers is genomic and epigenomic DNA alterations. Cancer cells acquire genetic and epigenetic alterations that drive the initiation and progression of the cancers by altering the molecular and cell biological process of the cells. These alterations, as well as other host and microenvironment factors, ultimately mediate the initiation and progression of cancers, including colorectal cancer. Epigenetic alterations, which include changes affecting DNA methylation, histone modifications, chromatin structure, and noncoding RNA expression, have emerged as a major class of molecular alteration in colon polyps and colorectal cancer. The classes of epigenetic alterations, their status in colorectal polyps and cancer, their effects on neoplasm biology, and their application to clinical care will be discussed.
Collapse
Affiliation(s)
- William M Grady
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Division of Gastroenterology, University of Washington School of Medicine, Seattle, WA, United States.
| |
Collapse
|
|
23
|
Ferlizza E, Solmi R, Sgarzi M, Ricciardiello L, Lauriola M. The Roadmap of Colorectal Cancer Screening. Cancers (Basel) 2021; 13:1101. [PMID: 33806465 PMCID: PMC7961708 DOI: 10.3390/cancers13051101] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 02/24/2021] [Accepted: 02/27/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. National screening programs based on fecal occult blood tests and subsequent colonoscopy have reduced the incidence and mortality, however improvements are needed since the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of the CRC screening globally and the state of the art in approaches aimed at improving accuracy and participation in CRC screening, also considering the need for gender and age differentiation. New fecal tests and biomarkers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel biomarkers and panels, such as circulating mRNA, micro- and long-non-coding RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods that could be easily applied to routine screening, or arrays and sequencing assays that should be better exploited to describe and identify candidate biomarkers in blood samples.
Collapse
Affiliation(s)
- Enea Ferlizza
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (R.S.); (M.S); (M.L.)
| | - Rossella Solmi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (R.S.); (M.S); (M.L.)
| | - Michela Sgarzi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (R.S.); (M.S); (M.L.)
| | - Luigi Ricciardiello
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy;
| | - Mattia Lauriola
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (R.S.); (M.S); (M.L.)
| |
Collapse
|
|
24
|
Grady WM, Yu M, Markowitz SD. Epigenetic Alterations in the Gastrointestinal Tract: Current and Emerging Use for Biomarkers of Cancer. Gastroenterology 2021; 160:690-709. [PMID: 33279516 PMCID: PMC7878343 DOI: 10.1053/j.gastro.2020.09.058] [Citation(s) in RCA: 147] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 09/24/2020] [Accepted: 09/28/2020] [Indexed: 02/06/2023]
Abstract
Colorectal cancer, liver cancer, stomach cancer, pancreatic cancer, and esophageal cancer are leading causes of cancer-related deaths worldwide. A fundamental trait of virtually all gastrointestinal cancers is genomic and epigenomic DNA alterations. Cancer cells acquire genetic and epigenetic alterations that drive the initiation and progression of the cancers by altering the molecular and cell biological processes of the cells. These alterations, as well as other host and microenvironment factors, ultimately mediate the clinical behavior of the precancers and cancers and can be used as biomarkers for cancer risk determination, early detection of cancer and precancer, determination of the prognosis of cancer and prediction of the response to therapy. Epigenetic alterations have emerged as one of most robust classes of biomarkers and are the basis for a growing number of clinical tests for cancer screening and surveillance.
Collapse
Affiliation(s)
- William M. Grady
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA,Division of Gastroenterology, University of Washington School of Medicine, Seattle, WA 98195, USA
| | - Ming Yu
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA
| | | |
Collapse
|
|
25
|
Barefoot ME, Lindberg MR, Wellstein A. Decoding the Tissue of Origin of Cellular Damage from Cell-Free DNA in Liquid Biopsies. SYSTEMS MEDICINE 2021. [DOI: 10.1016/b978-0-12-801238-3.11669-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
|
|
26
|
Cohen JD, Diergaarde B, Papadopoulos N, Kinzler KW, Schoen RE. Tumor DNA as a Cancer Biomarker through the Lens of Colorectal Neoplasia. Cancer Epidemiol Biomarkers Prev 2020; 29:2441-2453. [PMID: 33033144 PMCID: PMC7710619 DOI: 10.1158/1055-9965.epi-20-0549] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 07/06/2020] [Accepted: 09/30/2020] [Indexed: 12/24/2022] Open
Abstract
Biomarkers have a wide range of applications in the clinical management of cancer, including screening and therapeutic management. Tumor DNA released from neoplastic cells has become a particularly active area of cancer biomarker development due to the critical role somatic alterations play in the pathophysiology of cancer and the ability to assess released tumor DNA in accessible clinical samples, in particular blood (i.e., liquid biopsy). Many of the early applications of tumor DNA as a biomarker were pioneered in colorectal cancer due to its well-defined genetics and common occurrence, the effectiveness of early detection, and the availability of effective therapeutic options. Herein, in the context of colorectal cancer, we describe how the intended clinical application dictates desired biomarker test performance, how features of tumor DNA provide unique challenges and opportunities for biomarker development, and conclude with specific examples of clinical application of tumor DNA as a biomarker with particular emphasis on early detection.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."
Collapse
Affiliation(s)
- Joshua D Cohen
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Brenda Diergaarde
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
- UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Nickolas Papadopoulos
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kenneth W Kinzler
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Robert E Schoen
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| |
Collapse
|
|
27
|
Dudley JC, Diehn M. Detection and Diagnostic Utilization of Cellular and Cell-Free Tumor DNA. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2020; 16:199-222. [PMID: 33228464 DOI: 10.1146/annurev-pathmechdis-012419-032604] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Because cancer is caused by an accumulation of genetic mutations, mutant DNA released by tumors can be used as a highly specific biomarker for cancer. Although this principle was described decades ago, the advent and falling costs of next-generation sequencing have made the use of tumor DNA as a biomarker increasingly practical. This review surveys the use of cellular and cell-free DNA for the detection of cancer, with a focus on recent technological developments and applications to solid tumors. It covers (a) key principles and technology enabling the highly sensitive detection of tumor DNA; (b) assessment of tumor DNA in plasma, including for genotyping, minimal residual disease detection, and early detection of localized cancer; (c) detection of tumor DNA in body cavity fluids, such as urine or cerebrospinal fluid; and (d) challenges posed to the use of tumor DNA as a biomarker by the phenomenon of benign clonal expansions.
Collapse
Affiliation(s)
- Jonathan C Dudley
- Ludwig Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
| | - Maximilian Diehn
- Department of Radiation Oncology, Stanford Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA;
| |
Collapse
|
|
28
|
Sammarco G, Gallo G, Vescio G, Picciariello A, De Paola G, Trompetto M, Currò G, Ammendola M. Mast Cells, microRNAs and Others: The Role of Translational Research on Colorectal Cancer in the Forthcoming Era of Precision Medicine. J Clin Med 2020; 9:2852. [PMID: 32899322 PMCID: PMC7564551 DOI: 10.3390/jcm9092852] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 08/31/2020] [Accepted: 09/01/2020] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer (CRC) is a heterogeneous disease, molecularly and anatomically, that develops in a multi-step process requiring the accumulation of several genetic or epigenetic mutations that lead to the gradual transformation of normal mucosa into cancer. In fact, tumorigenesis is extremely complex, with many immunologic and non-immunologic factors present in the tumor microenvironment that can influence tumorigenesis. In the last few years, a role for mast cells (MCs), microRNAs (miRNAs), Kirsten rat sarcoma (KRAS) and v-raf murine sarcoma viral oncogene homologue B (BRAF) in cancer development and progression has been suggested, and numerous efforts have been made to thoroughly assess their correlation with CRC to improve patient survival and quality of life. The identification of easily measurable, non-invasive and cost-effective biomarkers, the so-called "ideal biomarkers", for CRC screening and treatment remains a high priority. The aim of this review is to discuss the emerging role of mast cells (MCs), microRNAs (miRNAs), KRAS and BRAF as diagnostic and prognostic biomarkers for CRC, evaluating their influence as potential therapy targets in the forthcoming era of precision medicine.
Collapse
Affiliation(s)
- Giuseppe Sammarco
- Department of Health Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.S.); (G.C.); (M.A.)
| | - Gaetano Gallo
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.V.); (G.D.P.)
| | - Giuseppina Vescio
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.V.); (G.D.P.)
| | - Arcangelo Picciariello
- Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, Piazza G Cesare, 11, 70124 Bari, Italy;
| | - Gilda De Paola
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.V.); (G.D.P.)
| | - Mario Trompetto
- Department of Colorectal Surgery, S. Rita Clinic, 13100 Vercelli, Italy;
| | - Giuseppe Currò
- Department of Health Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.S.); (G.C.); (M.A.)
| | - Michele Ammendola
- Department of Health Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.S.); (G.C.); (M.A.)
| |
Collapse
|
|
29
|
Kolenčík D, Shishido SN, Pitule P, Mason J, Hicks J, Kuhn P. Liquid Biopsy in Colorectal Carcinoma: Clinical Applications and Challenges. Cancers (Basel) 2020; 12:E1376. [PMID: 32471160 PMCID: PMC7352156 DOI: 10.3390/cancers12061376] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 05/16/2020] [Accepted: 05/25/2020] [Indexed: 12/24/2022] Open
Abstract
Colorectal carcinoma (CRC) is characterized by wide intratumor heterogeneity with general genomic instability and there is a need for improved diagnostic, prognostic, and therapeutic tools. The liquid biopsy provides a noninvasive route of sample collection for analysis of circulating tumor cells (CTCs) and genomic material, including cell-free DNA (cfDNA), as a complementary biopsy to the solid tumor tissue. The solid biopsy is critical for molecular characterization and diagnosis at the time of collection. The liquid biopsy has the advantage of longitudinal molecular characterization of the disease, which is crucial for precision medicine and patient-oriented treatment. In this review, we provide an overview of CRC and the different methodologies for the detection of CTCs and cfDNA, followed by a discussion on the potential clinical utility of the liquid biopsy in CRC patient care, and lastly, current challenges in the field.
Collapse
Affiliation(s)
- Drahomír Kolenčík
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech Republic; (D.K.); (P.P.)
| | - Stephanie N. Shishido
- Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; (S.N.S.); (J.M.); (J.H.)
| | - Pavel Pitule
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech Republic; (D.K.); (P.P.)
| | - Jeremy Mason
- Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; (S.N.S.); (J.M.); (J.H.)
- USC Institute of Urology, Catherine & Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - James Hicks
- Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; (S.N.S.); (J.M.); (J.H.)
| | - Peter Kuhn
- Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; (S.N.S.); (J.M.); (J.H.)
| |
Collapse
|
|
30
|
Ungerer V, Bronkhorst AJ, Holdenrieder S. Preanalytical variables that affect the outcome of cell-free DNA measurements. Crit Rev Clin Lab Sci 2020; 57:484-507. [DOI: 10.1080/10408363.2020.1750558] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Vida Ungerer
- Institute for Laboratory Medicine, German Heart Centre, Technical University Munich, Munich, Germany
| | - Abel J. Bronkhorst
- Institute for Laboratory Medicine, German Heart Centre, Technical University Munich, Munich, Germany
| | - Stefan Holdenrieder
- Institute for Laboratory Medicine, German Heart Centre, Technical University Munich, Munich, Germany
| |
Collapse
|
|
31
|
RAS Mutational Status Detection in Tissue, Plasma, and Stool Samples for Colorectal Cancer. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5419634. [PMID: 32351996 PMCID: PMC7174943 DOI: 10.1155/2020/5419634] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 03/21/2020] [Indexed: 12/18/2022]
Abstract
Objective RAS gene testing on tumor tissue biopsies is required for metastatic colorectal cancer (CRC) patients. However, it is infeasible for patients after curative surgery and repeated biopsy. This study is aimed at evaluating the consistency of RAS genes in patient's plasma, stool, and tumor tissue samples, to explore whether plasma and stool samples can supplement or replace tumor tissue to assess baseline RAS gene status. Methods Between June 2016 and October 2017, 53 patients with stage I-IV CRC from the Liaoning Cancer Hospital and the Department of Medical Oncology of the First Hospital of China Medical University were enrolled in the study. Patient tissues, peripheral blood, and stool samples were collected, and RAS gene tests were performed. Results Analysis of the KRAS gene in tissue, plasma, and stool samples from 53 CRC patients detected 25 cases (47%) of KRAS gene mutations in the tissue samples, 20 cases (38%) of KRAS gene mutations in plasma, and 18 (34%) KRAS gene mutations in fecal samples. The overall consistency of KRAS gene status between tissue samples and plasma samples was 77.4% (p ≤ 0.05) and between tissue samples and stool samples was 83% (p ≤ 0.05). In stage IV cases, the agreement of KRAS gene status between tissue and plasma samples was 93.8% (p ≤ 0.05) and 93.8% (p ≤ 0.05) between tissue and stool samples. Conclusion There was a high overall consistency in KRAS mutational assessment between plasma, stool, and tissue samples. In stage IV patients, the consistency of KRAS gene detection between tissue and stools or plasma was higher.
Collapse
|
|
32
|
Loktionov A. Biomarkers for detecting colorectal cancer non-invasively: DNA, RNA or proteins? World J Gastrointest Oncol 2020; 12:124-148. [PMID: 32104546 PMCID: PMC7031146 DOI: 10.4251/wjgo.v12.i2.124] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 10/30/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a global problem affecting millions of people worldwide. This disease is unique because of its slow progress that makes it preventable and often curable. CRC symptoms usually emerge only at advanced stages of the disease, consequently its early detection can be achieved only through active population screening, which markedly reduces mortality due to this cancer. CRC screening tests that employ non-invasively detectable biomarkers are currently being actively developed and, in most cases, samples of either stool or blood are used. However, alternative biological substances that can be collected non-invasively (colorectal mucus, urine, saliva, exhaled air) have now emerged as new sources of diagnostic biomarkers. The main categories of currently explored CRC biomarkers are: (1) Proteins (comprising widely used haemoglobin); (2) DNA (including mutations and methylation markers); (3) RNA (in particular microRNAs); (4) Low molecular weight metabolites (comprising volatile organic compounds) detectable by metabolomic techniques; and (5) Shifts in gut microbiome composition. Numerous tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically studied. While some of these studies generated promising early results, very few of the proposed tests have been transformed into clinically validated diagnostic/screening techniques. Such DNA-based tests as Food and Drug Administration-approved multitarget stool test (marketed as Cologuard®) or blood test for methylated septin 9 (marketed as Epi proColon® 2.0 CE) show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening tools. It can be concluded that, despite its deficiencies, the protein (haemoglobin) detection-based faecal immunochemical test (FIT) today presents the most cost-effective option for non-invasive CRC screening. The combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC screening. However, continuing intense research in the area promises the emergence of new superior non-invasive CRC screening tests that will allow the development of improved disease prevention strategies.
Collapse
|
|
33
|
Zhang M, Wei M, Dong Z, Duan H, Mao S, Feng S, Li W, Sun Z, Li J, Yan K, Liu H, Meng X, Ge H. Fecal DNA isolation and degradation in clam Cyclina sinensis: noninvasive DNA isolation for conservation and genetic assessment. BMC Biotechnol 2019; 19:99. [PMID: 31856784 PMCID: PMC6923993 DOI: 10.1186/s12896-019-0595-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 12/10/2019] [Indexed: 11/25/2022] Open
Abstract
Background To avoid destructive sampling for conservation and genetic assessment, we isolated the DNA of clam Cyclina sinensis from their feces. DNA electrophoresis and PCR amplification were used to determine the quality of fecal DNA. And we analyzed the effects of different conditions on the degradation of feces and fecal DNA. Results The clear fecal DNA bands were detected by electrophoresis, and PCR amplification using clam fecal DNA as template was effective and reliable, suggesting that clam feces can be used as an ideal material for noninvasive DNA isolation. In addition, by analyzing the effects of different environmental temperatures and soaking times on the degradation of feces and fecal DNA, we found that the optimum temperature was 4 °C. In 15 days, the feces maintained good texture, and the quality of fecal DNA was good. At 28 °C, the feces degraded in 5 days, and the quality of fecal DNA was poor. Conclusions The clam feces can be used as an ideal material for noninvasive DNA isolation. Moreover, the quality of fecal DNA is negatively correlated with environmental temperature and soaking time.
Collapse
Affiliation(s)
- Min Zhang
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Min Wei
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China.,Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Zhiguo Dong
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China. .,Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China.
| | - Haibao Duan
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Shuang Mao
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Senlei Feng
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Wenqian Li
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Zepeng Sun
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Jiawei Li
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Kanglu Yan
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Hao Liu
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Xueping Meng
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| | - Hongxing Ge
- Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China.,Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang, 222005, Jiangsu, China
| |
Collapse
|
|
34
|
Ding X, Yin K, Chen J, Wang K, Liu C. A ribonuclease-dependent cleavable beacon primer triggering DNA amplification for single nucleotide mutation detection with ultrahigh sensitivity and selectivity. Chem Commun (Camb) 2019; 55:12623-12626. [PMID: 31580354 DOI: 10.1039/c9cc06296c] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
We described a ribonuclease-dependent cleavable beacon primer, an energy-transfer-tagged oligonucleotide inserted with a ribonucleotide, which can be cleaved by ribonuclease to generate enhanced fluorescence signals and initiate DNA amplification for single nucleotide mutation detection with ultrahigh sensitivity and selectivity.
Collapse
Affiliation(s)
- Xiong Ding
- Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
| | - Kun Yin
- Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
| | - Ju Chen
- Department of Immunology, School of Medicine, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA
| | - Kepeng Wang
- Department of Immunology, School of Medicine, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA
| | - Changchun Liu
- Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
| |
Collapse
|
|
35
|
Abstract
Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Cross-sectional validation studies confirmed initial case-control studies' assessment of performance of an optimized multitarget stool DNA (mt-sDNA) test, leading to approval by the US Food and Drug Administration in 2014. Compared to colonoscopy, mt-sDNA showed sensitivity of 92% for detection of CRC, much higher than the 74% sensitivity of another recommended noninvasive strategy, fecal immunochemical testing (FIT). Detections of advanced adenomas and sessile serrated polyps were higher with mt-sDNA than FIT (42% versus 24% and 42% versus 5%, respectively), but overall specificity for all lesions was lower (87% versus 95%). The mt-sDNA test increases patient life-years gained in CRC screening simulations, but its cost relative to other screening strategies needs to be reduced by 80-90% or its sensitivity for polyp detection enhanced to be cost effective. Noninvasive CRC screening strategies such as fecal DNA, however, have the potential to significantly increase national screening rates due to their noninvasive nature and convenience for patients.
Collapse
Affiliation(s)
- John M Carethers
- Division of Gastroenterology and Hepatology, Department of Internal Medicine and Department of Human Genetics and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA;
| |
Collapse
|
|
36
|
Yu J, Xie Y, Li M, Zhou F, Zhong Z, Liu Y, Wang F, Qi J. Association between SFRP promoter hypermethylation and different types of cancer: A systematic review and meta-analysis. Oncol Lett 2019; 18:3481-3492. [PMID: 31516566 PMCID: PMC6733008 DOI: 10.3892/ol.2019.10709] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 06/04/2019] [Indexed: 02/06/2023] Open
Abstract
Abnormal methylation of secreted frizzled-related proteins (SFRPs) has been observed in various human cancer types. The loss of SFRP gene expression induces the activation of the Wnt pathway and is a vital mechanism for tumorigenesis and development. The aim of the present systematic review was to assess the association between SFRP methylation and cancer risk. A meta-analysis was systematically conducted to assess the clinicopathological significance of SFRP methylation in cancer risk. The Cochrane Library, PubMed and Web of Science databases were comprehensively searched, and 83 publications with a total of 21,612 samples were selected for the meta-analysis. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the degree of associations between SFRP promoter methylation and cancer risk. Subgroup analysis, meta regression and sensitivity analysis were used to identify the potential sources of heterogeneity. SFRP1, SFRP2, SFRP4 and SFRP5 hypermethylation was significantly associated with cancer risk, with ORs of 8.48 (95% CI, 6.26-11.49), 8.21 (95% CI, 6.20-10.88), 11.41 (95% CI, 6.42-20.30) and 6.34 (95% CI, 3.86-10.42), respectively. SFRP2 methylation was significantly associated with differentiation in colorectal cancer (OR, 2.16; 95% CI, 1.02-4.56). The results of the present study demonstrated that SFRP methylation may contribute to carcinogenesis, especially in certain cancer types, including hepatocellular carcinoma and colorectal cancer.
Collapse
Affiliation(s)
- Jun Yu
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.,Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Yang Xie
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.,Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Mengying Li
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.,Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Fenfang Zhou
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Zhenyang Zhong
- Department of Nephrology, Xingguo County People's Hospital, Ganzhou, Jiangxi 344000, P.R. China
| | - Yuting Liu
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.,Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Feng Wang
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.,Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Jian Qi
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.,Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| |
Collapse
|
|
37
|
Cell-Free DNA in the Liquid Biopsy Context: Role and Differences Between ctDNA and CTC Marker in Cancer Management. Methods Mol Biol 2019; 1909:47-73. [PMID: 30580422 DOI: 10.1007/978-1-4939-8973-7_4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Liquid biopsy is a new diagnostic concept to investigate the molecular features of solid tumors by blood, saliva, urine, and any other body fluids which show a source of potential biomarkers. In cancer patients, it is a simple and less invasive mean, representing a sustainable alternative to interrogate all tumor cells longitudinally, quantifying and characterizing the biological materials (DNAs, RNAs, proteins) which originate from cancer tissues. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) analysis from a simple blood draw received enormous attention for the related clinical research results. A rich scientific literature demonstrates that liquid biopsy is a valid instrument to assess the tumor biomarkers in real time and profile the cancer genotype in diagnostic and prognostic field, as well to quantify minimal residual disease, during patient follow-up. This could be a breakthrough for a companion diagnostic and personalized medicine. Liquid biopsy needs further implementation in the methodological aspects as well as cost-based assessment. The number of new molecular diagnostic assays increases day by day, but the standards for their adoption and clinical validation are still to be achieved.
Collapse
|
|
38
|
Fu Y, Duan X, Huang J, Huang L, Zhang L, Cheng W, Ding S, Min X. Detection of KRAS mutation via ligation-initiated LAMP reaction. Sci Rep 2019; 9:5955. [PMID: 30976068 PMCID: PMC6459849 DOI: 10.1038/s41598-019-42542-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Accepted: 04/03/2019] [Indexed: 02/06/2023] Open
Abstract
KRAS mutations are abnormalities widely found in genomic DNA and circulating tumor DNA (ctDNA) of various types of cancers. Thus, highly sensitive detection of KRAS mutations in genomic DNA is of great significance in disease diagnosis and personalized medicine. Here, we developed a ligation-initiated loop-mediated isothermal amplification (LAMP) assaying method for ultrasensitive detection of KRAS mutation. In the presence of mutant KRAS DNA (mutDNA), the dumbbell-shaped structure (DSS) is formed by the specific ligation of two substrates (SLS1 and SLS2), which act as a template to initiate the following LAMP amplification. Making use of the outstanding specificity of ligation reaction and superior amplification of LAMP, 10 aM mutDNA can be accurately determined. In addition, as low as 0.1% mutDNA can be detected in the presence of a large excess of wild-type KRAS DNA (wtDNA), indicating the high sensitivity and specificity of the method. Furthermore, this strategy has been successfully applied for detection of a KRAS mutation from tissue samples of colorectal cancer patients. Thus, the developed ligation-initiated LAMP fluorescence assaying strategy presents a promising prospect for ultrasensitive detection of mutations.
Collapse
Affiliation(s)
- Yixin Fu
- Department of Laboratory Medicine, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, P.R. China.,School of Laboratory Medicine, Zunyi Medical University, Zunyi, 563003, P.R. China
| | - Xiaolei Duan
- School of Laboratory Medicine, Zunyi Medical University, Zunyi, 563003, P.R. China.,Key Laboratory of Clinical Laboratory Diagnostics (Ministry of education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400010, P.R. China
| | - Jian Huang
- Department of Laboratory Medicine, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, P.R. China.,School of Laboratory Medicine, Zunyi Medical University, Zunyi, 563003, P.R. China
| | - Lizhen Huang
- The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, P.R. China
| | - Lutan Zhang
- The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, P.R. China
| | - Wei Cheng
- The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, P.R. China
| | - Shijia Ding
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400010, P.R. China
| | - Xun Min
- Department of Laboratory Medicine, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, P.R. China. .,School of Laboratory Medicine, Zunyi Medical University, Zunyi, 563003, P.R. China.
| |
Collapse
|
|
39
|
Bronkhorst AJ, Ungerer V, Holdenrieder S. The emerging role of cell-free DNA as a molecular marker for cancer management. BIOMOLECULAR DETECTION AND QUANTIFICATION 2019; 17:100087. [PMID: 30923679 PMCID: PMC6425120 DOI: 10.1016/j.bdq.2019.100087] [Citation(s) in RCA: 367] [Impact Index Per Article: 61.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 02/26/2019] [Accepted: 03/11/2019] [Indexed: 02/07/2023]
Abstract
An increasing number of studies demonstrate the potential use of cell-free DNA (cfDNA) as a surrogate marker for multiple indications in cancer, including diagnosis, prognosis, and monitoring. However, harnessing the full potential of cfDNA requires (i) the optimization and standardization of preanalytical steps, (ii) refinement of current analysis strategies, and, perhaps most importantly, (iii) significant improvements in our understanding of its origin, physical properties, and dynamics in circulation. The latter knowledge is crucial for interpreting the associations between changes in the baseline characteristics of cfDNA and the clinical manifestations of cancer. In this review we explore recent advancements and highlight the current gaps in our knowledge concerning each point of contact between cfDNA analysis and the different stages of cancer management.
Collapse
Affiliation(s)
| | | | - Stefan Holdenrieder
- Institute for Laboratory Medicine, German Heart Centre, Technical University Munich, Lazarettstraße. 36, D-80636, Munich, Germany
| |
Collapse
|
|
40
|
Vymetalkova V, Cervena K, Bartu L, Vodicka P. Circulating Cell-Free DNA and Colorectal Cancer: A Systematic Review. Int J Mol Sci 2018; 19:ijms19113356. [PMID: 30373199 PMCID: PMC6274807 DOI: 10.3390/ijms19113356] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 10/22/2018] [Accepted: 10/24/2018] [Indexed: 02/06/2023] Open
Abstract
There is a strong demand for the identification of new biomarkers in colorectal cancer (CRC) diagnosis. Among all liquid biopsy analysts, cell-free circulating DNA (cfDNA) is probably the most promising tool with respect to the identification of minimal residual diseases, assessment of treatment response and prognosis, and identification of resistance mechanisms. Circulating cell-free tumor DNA (ctDNA) maintains the same genomic signatures that are present in the matching tumor tissue allowing for the quantitative and qualitative evaluation of mutation burdens in body fluids. Thus, ctDNA-based research represents a non-invasive method for cancer detection. Among the numerous possible applications, the diagnostic, predictive, and/or prognostic utility of ctDNA in CRC has attracted intense research during the last few years. In the present review, we will describe the different aspects related to cfDNA research and evidence from studies supporting its potential use in CRC diagnoses and the improvement of therapy efficacy. We believe that ctDNA-based research should be considered as key towards the introduction of personalized medicine and patient benefits.
Collapse
Affiliation(s)
- Veronika Vymetalkova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 00 Prague, Czech Republic.
- Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00 Prague, Czech Republic.
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, 323 00 Pilsen, Czech Republic.
| | - Klara Cervena
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 00 Prague, Czech Republic.
- Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00 Prague, Czech Republic.
| | - Linda Bartu
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 00 Prague, Czech Republic.
- Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00 Prague, Czech Republic.
| | - Pavel Vodicka
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 00 Prague, Czech Republic.
- Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00 Prague, Czech Republic.
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, 323 00 Pilsen, Czech Republic.
| |
Collapse
|
|
41
|
Sidransky D. First Person: David Sidransky, MD: Clinician-Scientist Transforms Cancer Early Detection. Cancer 2018; 124:3077-3078. [PMID: 30117596 DOI: 10.1002/cncr.31653] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
|
|
42
|
Ma Y, Yates JR. Proteomics and pulse azidohomoalanine labeling of newly synthesized proteins: what are the potential applications? Expert Rev Proteomics 2018; 15:545-554. [PMID: 30005169 PMCID: PMC6329588 DOI: 10.1080/14789450.2018.1500902] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Measuring the immediate changes in cells that arise from changing environmental conditions is crucial to understanding the underlying mechanisms involved. These changes can be measured with metabolic stable isotope fully labeled proteomes, but requires looking for changes in the midst of a large background. In addition, labeling efficiency can be an issue in primary and fully differentiated cells. Area covered: Azidohomoalanine (AHA), an analog of methionine, can be accepted by cellular translational machinery and incorporated into newly synthesized proteins (NSPs). AHA-NSPs can be coupled to biotin via CuAAC-mediated click-chemistry and enriched using avidin-based affinity purification. Thus, AHA-containing proteins or peptides can be enriched and efficiently separated from the whole proteome. In this review, we describe the development of mass spectrometry (MS) based AHA strategies and discuss their potential to measure proteins involved in immune response, secretome, gut microbiome, and proteostasis as well as their potential for clinical uses. Expert commentary: AHA strategies have been used to identify synthesis activity and to compare two biological conditions in various biological model organisms. In combination with instrument development, improved sample preparation and fractionation strategies, MS-based AHA strategies have the potential for broad application, and the methods should translate into clinical use.
Collapse
Affiliation(s)
- Yuanhui Ma
- a Departments of Molecular Medicine and Neurobiology , The Scripps Research Institute , La Jolla , CA , USA
| | - John R Yates
- a Departments of Molecular Medicine and Neurobiology , The Scripps Research Institute , La Jolla , CA , USA
| |
Collapse
|
|
43
|
Hui Y, Wu Z, Qin Z, Zhu L, Liang J, Li X, Fu H, Feng S, Yu J, He X, Lu W, Xiao W, Wu Q, Zhang B, Zhao W. Micro-droplet Digital Polymerase Chain Reaction and Real-Time Quantitative Polymerase Chain Reaction Technologies Provide Highly Sensitive and Accurate Detection of Zika Virus. Virol Sin 2018; 33:270-277. [PMID: 29931514 PMCID: PMC6178550 DOI: 10.1007/s12250-018-0037-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 05/23/2018] [Indexed: 12/21/2022] Open
Abstract
The establishment of highly sensitive diagnostic methods is critical in the early diagnosis and control of Zika virus (ZIKV) and in preventing serious neurological complications of ZIKV infection. In this study, we established micro-droplet digital polymerase chain reaction (ddPCR) and real-time quantitative PCR (RT-qPCR) protocols for the detection of ZIKV based on the amplification of the NS5 gene. For the ZIKV standard plasmid, the RT-qPCR results showed that the cycle threshold (Ct) value was linear from 101 to 108 copy/μL, with a standard curve R2 of 0.999 and amplification efficiency of 92.203%; however, a concentration as low as 1 copy/μL could not be detected. In comparison with RT-qPCR, the ddPCR method resulted in a linear range of 101-104 copy/μL and was able to detect concentrations as low as 1 copy/μL. Thus, for detecting ZIKV from clinical samples, RT-qPCR is a better choice for high-concentration samples (above 101 copy/μL), while ddPCR has excellent accuracy and sensitivity for low-concentration samples. These results indicate that the ddPCR method should be of considerable use in the early diagnosis, laboratory study, and monitoring of ZIKV.
Collapse
Affiliation(s)
- Yuan Hui
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Zhiming Wu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Zhiran Qin
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Li Zhu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Junhe Liang
- Jiangmen Center for Disease Control and Prevention, Jiangmen, 529085, China
| | - Xujuan Li
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Hanmin Fu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Shiyu Feng
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Jianhai Yu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Xiaoen He
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Weizhi Lu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Weiwei Xiao
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Qinghua Wu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Bao Zhang
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
| | - Wei Zhao
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
- Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmacy, Southern Medical University, Guangzhou, 510515, China.
| |
Collapse
|
|
44
|
Wu X, Zhu L, Ma PC. Next-Generation Novel Noninvasive Cancer Molecular Diagnostics Platforms Beyond Tissues. Am Soc Clin Oncol Educ Book 2018; 38:964-977. [PMID: 30231325 PMCID: PMC6381937 DOI: 10.1200/edbk_199767] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In recent years, there has been a revolutionary expansion in technologic advances and therapeutic innovations in cancer medicine. Cancer diagnostics has begun to move away from a sole dependence on direct tumor tissue biopsy for cancer detection, diagnosis, and treatment monitoring. The need for improvement in molecular cancer diagnostics has never been more important, with not only the advent of cancer genomics and genomics-guided precision medicine but also the recent arrival of cancer immunotherapies. Owing to the practical limitations and risks associated with tissue-based biopsy diagnostics, novel noninvasive cancer diagnostics platforms have continued to evolve and expand in recent years. Examples of these platforms include the liquid biopsy, which is used to interrogate ctDNA or circulating tumor cells, proteomics, metabolomics, and exosomes; the urine biopsy, which is used to assay ctDNAs; saliva and stool biopsies, which are used for molecular genomics assays; and the breath biopsy, which measures volatile organic compounds. These next-generation noninvasive molecular diagnostics assays beyond tissues fundamentally transform the potential utilities of cancer diagnostics to enable repeat, prospective, and serial longitudinal "biopsies" to monitor disease response resistance and progression on therapies. Moreover, they allow continual interrogation and molecular in-depth analysis of the evolving tumor's pan-canceromics under therapeutic stress. These technological and diagnostic advances have already brought about paradigm-changing next-generation cancer therapeutic strategies to enhance overall treatment efficacies. This article reviews the key noninvasive next-generation molecular diagnostics platforms beyond tissues, with emphasis on clinical utilities and applications.
Collapse
Affiliation(s)
- Xiaoliang Wu
- From the West Virginia University Cancer Institute, West Virginia University Medicine, West Virginia University, Morgantown, WA; West Virginia Clinical and Translational Institute, Morgantown, WV
| | - Lin Zhu
- From the West Virginia University Cancer Institute, West Virginia University Medicine, West Virginia University, Morgantown, WA; West Virginia Clinical and Translational Institute, Morgantown, WV
| | - Patrick C Ma
- From the West Virginia University Cancer Institute, West Virginia University Medicine, West Virginia University, Morgantown, WA; West Virginia Clinical and Translational Institute, Morgantown, WV
| |
Collapse
|
|
45
|
Salk JJ, Schmitt MW, Loeb LA. Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations. Nat Rev Genet 2018; 19:269-285. [PMID: 29576615 PMCID: PMC6485430 DOI: 10.1038/nrg.2017.117] [Citation(s) in RCA: 351] [Impact Index Per Article: 50.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Mutations, the fuel of evolution, are first manifested as rare DNA changes within a population of cells. Although next-generation sequencing (NGS) technologies have revolutionized the study of genomic variation between species and individual organisms, most have limited ability to accurately detect and quantify rare variants among the different genome copies in heterogeneous mixtures of cells or molecules. We describe the technical challenges in characterizing subclonal variants using conventional NGS protocols and the recent development of error correction strategies, both computational and experimental, including consensus sequencing of single DNA molecules. We also highlight major applications for low-frequency mutation detection in science and medicine, describe emerging methodologies and provide our vision for the future of DNA sequencing.
Collapse
Affiliation(s)
- Jesse J Salk
- Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA
- Department of Medicine, Divisions of Hematology and Medical Oncology, University of Washington School of Medicine, Seattle, WA, USA
- Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA
| | - Michael W Schmitt
- Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA
- Department of Medicine, Divisions of Hematology and Medical Oncology, University of Washington School of Medicine, Seattle, WA, USA
- Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA
| | - Lawrence A Loeb
- Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA
- Department of Biochemistry, University of Washington School of Medicine, Seattle, WA, USA
| |
Collapse
|
|
46
|
Abstract
A general synthetic overview of the process of carcinogenesis is presented. The following points are discussed: the uniqueness of tumor disease with respect to other pathologies; tumors viewed as a pathology of the transduction system of signals that regulate the communal life of the cells of multicell organisms; the tumor as a genetic disease of somatic cells; carcinogenesis as a multistage event; the fundamental role of physiologic and pathologic rhythms of cell proliferation in the modulation of tumor incidence; mechanisms entailed in the maintenance of genome integrity; mechanisms involved in the protection of genome integrity from exogenous and endogenous causes of degradation of the genetic message.
Collapse
Affiliation(s)
- S Parodi
- National Institute for Cancer Research, Genoa, Italy
| | | |
Collapse
|
|
47
|
Margetis N, Kouloukoussa M, Pavlou K, Vrakas S, Mariolis-Sapsakos T. K- ras Mutations as the Earliest Driving Force in a Subset of Colorectal Carcinomas. ACTA ACUST UNITED AC 2018; 31:527-542. [PMID: 28652417 DOI: 10.21873/invivo.11091] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Revised: 05/18/2017] [Accepted: 05/22/2017] [Indexed: 12/12/2022]
Abstract
K-ras oncogene is a key factor in colorectal cancer. Based on published and our data we propose that K-ras could be the oncogene responsible for the inactivation of the tumor-suppressor gene APC, currently considered as the initial step in colorectal tumorigenesis. K-ras fulfills the criteria of the oncogene-induced DNA damage model, as it can provoke well-established causes for inactivating tumor-suppressors, i.e. DNA double-strand breaks (causing allele deletion) and ROS production (responsible for point mutation). The model we propose is a variation of the currently existing model and hypothesizes that, in a subgroup of colorectal carcinomas, K-ras mutation may precede APC inactivation, representing the earliest driving force and, probably, an early biomarker of colorectal carcinogenesis. This observation is clinically useful, since it may modify the preventive colorectal cancer strategy, restricting numerically patients undergoing colonoscopies to those bearing K-ras mutation in their colorectum, either in benign polyps or the normal accompanying mucosa.
Collapse
Affiliation(s)
- Nikolaos Margetis
- "Athens Euroclinic", Athens, Greece .,Molecular Carcinogenesis Group, Laboratory of Histology and Embryology, Medical School, University of Athens, Athens, Greece
| | - Myrsini Kouloukoussa
- Molecular Carcinogenesis Group, Laboratory of Histology and Embryology, Medical School, University of Athens, Athens, Greece
| | - Kyriaki Pavlou
- Molecular Carcinogenesis Group, Laboratory of Histology and Embryology, Medical School, University of Athens, Athens, Greece
| | | | | |
Collapse
|
|
48
|
Plagnol V, Woodhouse S, Howarth K, Lensing S, Smith M, Epstein M, Madi M, Smalley S, Leroy C, Hinton J, de Kievit F, Musgrave-Brown E, Herd C, Baker-Neblett K, Brennan W, Dimitrov P, Campbell N, Morris C, Rosenfeld N, Clark J, Gale D, Platt J, Calaway J, Jones G, Forshew T. Analytical validation of a next generation sequencing liquid biopsy assay for high sensitivity broad molecular profiling. PLoS One 2018; 13:e0193802. [PMID: 29543828 PMCID: PMC5854321 DOI: 10.1371/journal.pone.0193802] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 02/20/2018] [Indexed: 12/21/2022] Open
Abstract
Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA. The assay has been developed to detect point mutations, indels, amplifications and gene fusions that commonly occur in NSCLC. For analytical validation, two 10mL blood tubes were collected from NSCLC patients and healthy volunteer donors. In addition, contrived samples were used to represent a wide spectrum of genetic aberrations and VAFs. Samples were analyzed by multiple operators, at different times and using different reagent Lots. Results were compared with digital PCR (dPCR). The InVisionFirst assay demonstrated an excellent limit of detection, with 99.48% sensitivity for SNVs present at VAF range 0.25%-0.33%, 92.46% sensitivity for indels at 0.25% VAF and a high rate of detection at lower frequencies while retaining high specificity (99.9997% per base). The assay also detected ALK and ROS1 gene fusions, and DNA amplifications in ERBB2, FGFR1, MET and EGFR with high sensitivity and specificity. Comparison between the InVisionFirst assay and dPCR in a series of cancer patients showed high concordance. This analytical validation demonstrated that the InVisionFirst assay is highly sensitive, specific and robust, and meets analytical requirements for clinical applications.
Collapse
Affiliation(s)
- Vincent Plagnol
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Samuel Woodhouse
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Karen Howarth
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Stefanie Lensing
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Matt Smith
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Michael Epstein
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Mikidache Madi
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Sarah Smalley
- Product Development, Inivata Inc, Research Triangle Park, North Carolina, United States of America
| | - Catherine Leroy
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Jonathan Hinton
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Frank de Kievit
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | | | - Colin Herd
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Katherine Baker-Neblett
- Clinical Development, Inivata Inc, Research Triangle Park, North Carolina, United States of America
| | - Will Brennan
- Product Development, Inivata Inc, Research Triangle Park, North Carolina, United States of America
| | - Peter Dimitrov
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Nathan Campbell
- Clinical Laboratory Operations, Inivata Inc, Research Triangle Park, North Carolina, United States of America
| | - Clive Morris
- Clinical Development, Inivata Inc, Research Triangle Park, North Carolina, United States of America
| | - Nitzan Rosenfeld
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - James Clark
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Davina Gale
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| | - Jamie Platt
- Product Development, Inivata Inc, Research Triangle Park, North Carolina, United States of America
| | - John Calaway
- Product Development, Inivata Inc, Research Triangle Park, North Carolina, United States of America
| | - Greg Jones
- Product Development, Inivata Inc, Research Triangle Park, North Carolina, United States of America
| | - Tim Forshew
- Research and Development, Inivata Ltd, Granta Park, Cambridge, United Kingdom
| |
Collapse
|
|
49
|
Labianca R, Merelli B. Screening and Diagnosis for Colorectal Cancer: Present and Future. TUMORI JOURNAL 2018. [DOI: 10.1177/548.6506] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
| | - Barbara Merelli
- Unit of Medical Oncology, Ospedali Riuniti di Bergamo, Italy
| |
Collapse
|
|
50
|
Krylov NN, Pyatenko EA, Komissarov AB. [Comparative analysis of colorectal cancer screening approaches]. Khirurgiia (Mosk) 2017:92-97. [PMID: 29186105 DOI: 10.17116/hirurgia20171192-97] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- N N Krylov
- First Moscow State medical University named after I.M. Sechenov, Moscow, Russia
| | - E A Pyatenko
- First Moscow State medical University named after I.M. Sechenov, Moscow, Russia
| | - A B Komissarov
- First Moscow State medical University named after I.M. Sechenov, Moscow, Russia
| |
Collapse
|