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1
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Carvalho B, de Klaver W, van Wifferen F, van Lanschot MCJ, van Wetering AJP, van der Zander QEW, Lemmens M, Bolijn AS, Tijssen M, Delis-van Diemen P, Buekers N, Daenen K, van der Meer J, van Mulligen PG, Hijmans BS, de Ridder S, Meiqari L, Bierkens M, van der Hulst RWM, Kuyvenhoven JPH, van Berkel AM, Depla ACTM, van Leerdam ME, Jansen JM, Wientjes CA, Straathof JWA, Keulen ETP, Ramsoekh D, Moons LMG, Zacherl M, Masclee AAM, de Wit M, Greuter MJE, van Engeland M, Dekker E, Coupé VMH, Meijer GA. Stool-Based Testing for Post-Polypectomy Colorectal Cancer Surveillance Safely Reduces Colonoscopies: The MOCCAS Study. Gastroenterology 2025; 168:121-135.e16. [PMID: 39218164 DOI: 10.1053/j.gastro.2024.08.022] [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: 08/10/2023] [Revised: 07/23/2024] [Accepted: 08/05/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND & AIMS Colonoscopy-based surveillance to prevent colorectal cancer (CRC) causes substantial burden for patients and health care. Stool tests may help to reduce surveillance colonoscopies by limiting colonoscopies to individuals at increased risk of advanced neoplasia. METHODS This cross-sectional observational study included individuals aged 50-75 years with surveillance indication. Before bowel preparation, participants collected samples for a multitarget stool DNA test and 2 fecal immunochemical tests (FITs). Test accuracy was calculated for all surveillance indications. For the post-polypectomy indication only, which is the most common and is associated with a relatively low CRC risk, long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer (ASCCA) model. Stool-based strategies were simulated to tune each test's positivity threshold to obtain strategies at least as effective as colonoscopy surveillance. RESULTS There were 3453 individuals with results for all stool tests and colonoscopy; 2226 had previous polypectomy, 1003 had previous CRC, and 224 had a familial risk. Areas under the receiver operating characteristic curve for advanced neoplasia were 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test, 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR (Eiken Chemical Co, Tokyo, Japan) and 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold (Sentinel, Milan, Italy). Stool-based post-polypectomy surveillance strategies at least as effective as colonoscopy surveillance reduced the number of colonoscopies by 15%-41% and required 5.6-9.5 stool tests over a person's lifetime. Multitarget stool DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs. CONCLUSIONS This study found that stool-based post-polypectomy surveillance strategies can be safe and cost-effective, with potential to reduce the number of colonoscopies by up to 41%. CLINICALTRIALS gov, Number: NCT02715141.
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Affiliation(s)
- Beatriz Carvalho
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Willemijn de Klaver
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, The Netherlands
| | - Francine van Wifferen
- Department of Epidemiology and Data Science, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, The Netherlands
| | - Meta C J van Lanschot
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, The Netherlands
| | - Alouisa J P van Wetering
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Quirine E W van der Zander
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Margriet Lemmens
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Anne S Bolijn
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marianne Tijssen
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | | | - Nikkie Buekers
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Kathleen Daenen
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Jaleesa van der Meer
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
| | | | - Brenda S Hijmans
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Sander de Ridder
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Lana Meiqari
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Mariska Bierkens
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - René W M van der Hulst
- Department of Gastroenterology and Hepatology, Spaarne Gasthuis, Haarlem, The Netherlands
| | - Johan P H Kuyvenhoven
- Department of Gastroenterology and Hepatology, Spaarne Gasthuis, Haarlem, The Netherlands
| | - Annemarie M van Berkel
- Department of Gastroenterology and Hepatology, Noordwest Ziekenhuis, Alkmaar, The Netherlands
| | - Annekatrien C T M Depla
- Department of Gastroenterology and Hepatology, Slotervaartziekenhuis, Amsterdam, The Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jeroen M Jansen
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Caroline A Wientjes
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Jan W A Straathof
- Department of Gastroenterology and Hepatology, Maxima Medisch Centrum, Veldhoven, The Netherlands
| | - Eric T P Keulen
- Department of Gastroenterology and Hepatology, Zuyderland Medisch Centrum, Sittard-Geleen, The Netherlands
| | - Dewkoemar Ramsoekh
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, The Netherlands
| | - Leon M G Moons
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Ad A M Masclee
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Meike de Wit
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marjolein J E Greuter
- Department of Epidemiology and Data Science, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, The Netherlands
| | - Manon van Engeland
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, The Netherlands
| | - Veerle M H Coupé
- Department of Epidemiology and Data Science, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, The Netherlands
| | - Gerrit A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
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van Wifferen F, Greuter MJE, van Leerdam ME, Spanier MBW, Dekker E, Vasen HFA, Lansdorp-Vogelaar I, Canfell K, Meijer GA, Bisseling TM, Hoogerbrugge N, Coupé VMH. Combining Colonoscopy With Fecal Immunochemical Test Can Improve Current Familial Colorectal Cancer Colonoscopy Surveillance: A Modelling Study. Gastroenterology 2025; 168:136-149. [PMID: 39214503 DOI: 10.1053/j.gastro.2024.08.025] [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: 04/22/2024] [Revised: 07/22/2024] [Accepted: 08/13/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND & AIMS The authors assessed whether familial colorectal cancer (FCRC) surveillance in individuals without hereditary CRC can be optimized METHODS: The Adenoma and Serrated Pathway to Colorectal Cancer (ASCCA)-FCRC model simulates CRC development in individuals with a family history of CRC at 2-fold and 4-fold increased CRC risk compared with the general population. The authors simulated a strategy without surveillance, the current Dutch guideline (5-yearly colonoscopy between ages 45 and 75 years), and the following 3 sets of alternative strategies: colonoscopy surveillance, surveillance combining colonoscopy and fecal immunochemical testing (FIT), and FIT-based surveillance. Each set included a range of strategies differing in age range and test interval. The optimal strategy was defined as the strategy with highest quality-adjusted life-years (QALYs) satisfying all of the following criteria: in the (near-)efficiency area of the cost-effectiveness frontier and compared with current surveillance; noninferior effectiveness; no substantial increase in colonoscopy burden; and not more expensive. RESULTS The optimal strategy was 10-yearly colonoscopy with 2-yearly FIT between colonoscopies from ages 40 to 80 years for both 2-fold and 4-fold increased CRC risk. At 2-fold risk, this strategy prevented 0.8 more CRC deaths, gained 15.8 more QALYs at 731 fewer colonoscopies, and saved €98,000 over the lifetime of 1000 individuals compared with current surveillance. At 4-fold risk, figures were 2.1 more CRC deaths prevented, 37.0 more QALYs gained at 567 fewer colonoscopies, and €127,000 lower costs. Current surveillance was not (near-)efficient. CONCLUSIONS FIT could play an important role in FCRC surveillance. Surveillance with 10-yearly colonoscopy and 2-yearly FIT between colonoscopies from ages 40 to 80 years increased QALYs and reduced colonoscopy burden and costs compared with current FCRC surveillance.
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Affiliation(s)
- Francine van Wifferen
- Decision Modeling Center, Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam Public Health, Amsterdam, The Netherlands.
| | - Marjolein J E Greuter
- Decision Modeling Center, Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam Public Health, Amsterdam, The Netherlands
| | - Monique E van Leerdam
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Marcel B W Spanier
- Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Hans F A Vasen
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands
| | - Karen Canfell
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council New South Wales, New South Wales, Sydney, Australia
| | - Gerrit A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Tanya M Bisseling
- Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Nicoline Hoogerbrugge
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Veerle M H Coupé
- Decision Modeling Center, Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam Public Health, Amsterdam, The Netherlands
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Clarke JA, Benning J, Isaacs J, Angell-Clarke S. A balance of clinical assessment and use of diagnostic imaging: A CT colonography comparative case report. Radiol Case Rep 2024; 19:2751-2755. [PMID: 38680738 PMCID: PMC11047173 DOI: 10.1016/j.radcr.2024.03.066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/09/2024] [Accepted: 03/25/2024] [Indexed: 05/01/2024] Open
Abstract
Computer tomography colonography (CTC) is a non-invasive procedure which has replaced barium enema. CTC uses helical images of a cleansed and gas-distended colon for the diagnosis and treatment of colonic neoplasms. This case study compares 2 patients: one with positive pathology (patient A) and another as comparator (patient B) with a similar pathology to discuss and debate possible treatment pathways. Patient (A) CTC showed 2 polyps: 6 mm and 10 mm, which the colorectal surgeons thought only needed follow-up. Our comparator (patient B) displayed a similar pathology which measured 9 mm. In this case (patient B), there was mutual agreement with the surgeons for polypectomy but without haematology involvement which was atypical of the usual pathway. The surgeons did not see the 9 mm polyp at polypectomy which could be due to observer error or radiology reporter error. Given that conventional colonoscopy is more sensitive in detecting polyps; a repeat of both tests could confirm the presence of polyp, however, the surgeons gave patient (B) a virtual appointment and requested a repeat CTC in 12 months. In colorectal medicine there can be variations in the treatment of patients with polyps. While a repeat of both tests could confirm the presence of polyp in patient (B), the surgeons' decisions regarding the patient's treatment reflected a balance of confidence in clinical assessment and use of diagnostic imaging which can reduce unnecessary requests and use of diagnostic tests.
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Affiliation(s)
- Justin A. Clarke
- Ashford and St. Peter's Hospitals Radiology Department, Guilford Road, Chertsey, Surrey, UK
| | - Jeevon Benning
- Ashford and St. Peter's Hospitals Radiology Department, Guilford Road, Chertsey, Surrey, UK
| | - John Isaacs
- Ashford and St. Peter's Hospitals Research and Development Department, Guilford Road, Chertsey, Surrey, UK
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Shuai Y, Ma Z, Ju J, Wei T, Gao S, Kang Y, Yang Z, Wang X, Yue J, Yuan P. Liquid-based biomarkers in breast cancer: looking beyond the blood. J Transl Med 2023; 21:809. [PMID: 37957623 PMCID: PMC10644618 DOI: 10.1186/s12967-023-04660-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
In recent decades, using circulating tumor cell (CTC), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), exosomes and etc. as liquid biomarkers has received enormous attention in various tumors, including breast cancer (BC). To date, efforts in the area of liquid biopsy predominantly focus on the analysis of blood-based markers. It is worth noting that the identifications of markers from non-blood sources provide unique advantages beyond the blood and these alternative sources may be of great significance in offering supplementary information in certain settings. Here, we outline the latest advances in the analysis of non-blood biomarkers, predominantly including urine, saliva, cerebrospinal fluid, pleural fluid, stool and etc. The unique advantages of such testings, their current limitations and the appropriate use of non-blood assays and blood assays in different settings are further discussed. Finally, we propose to highlight the challenges of these alternative assays from basic to clinical implementation and explore the areas where more investigations are warranted to elucidate its potential utility.
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Affiliation(s)
- You Shuai
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhonghua Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Endoscopy, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Jie Ju
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Tong Wei
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Songlin Gao
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yikun Kang
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zixuan Yang
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xue Wang
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jian Yue
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Peng Yuan
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Chiu LS, Calderwood AH. Noninvasive Colorectal Cancer Prevention Options in Older Adults. J Clin Gastroenterol 2023; 57:855-862. [PMID: 37436836 DOI: 10.1097/mcg.0000000000001893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide and its incidence increases with age. The proportion of older adults in the United States continues to rise, making CRC prevention a key health priority for our aging population. CRC is a largely preventable disease through screening and polyp surveillance, and noninvasive modalities represent an important option for older adults in whom the burdens and risks of invasive testing are higher compared with younger adults. This review highlights the evidence, risks, and benefits of noninvasive CRC screening and surveillance options in older adults and discusses the challenges of CRC prevention in this cohort.
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Affiliation(s)
- Laura S Chiu
- Department of Medicine, Section of Gastroenterology, Boston University School of Medicine, Boston, MA
| | - Audrey H Calderwood
- Department of Medicine, Section of Gastroenterology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
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East JE. Risk Classification After Colonoscopy and Polypectomy: Are We Always Fighting the Last War? Gastroenterology 2023; 165:333-335. [PMID: 37245590 DOI: 10.1053/j.gastro.2023.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 04/23/2023] [Indexed: 05/30/2023]
Affiliation(s)
- James E East
- Translational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; Division of Gastroenterology and Hepatology, Mayo Clinic Healthcare, London, United Kingdom.
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Ykema BL, Gini A, Rigter LS, Spaander MC, Moons LM, Bisseling TM, de Boer JP, Verbeek WH, Lugtenburg PJ, Janus CP, Petersen EJ, Roesink JM, van der Maazen RW, for the DICHOS study group, Aleman BM, Meijer GA, van Leeuwen FE, Snaebjornsson P, Carvalho B, van Leerdam ME, Lansdorp-Vogelaar I. Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy. Cancer Epidemiol Biomarkers Prev 2022; 31:2157-2168. [PMID: 36166472 PMCID: PMC9720424 DOI: 10.1158/1055-9965.epi-22-0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 05/19/2022] [Accepted: 09/13/2022] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups. METHODS The Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal immunochemical test (FIT, OC-Sensor; cutoffs: 10/20/47 μg Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of €20,000 per life-years gained (LYG). RESULTS Overall, the optimal surveillance strategy was annual FIT (47 μg) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:€18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 μg) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER:€15,000/LYG), and when treated with IRT and procarbazine, annual FIT (47 μg) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:€13,000/LYG). CONCLUSIONS Colorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy. IMPACT Colorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors.
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Affiliation(s)
- Berbel L.M. Ykema
- Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Andrea Gini
- Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Lisanne S. Rigter
- Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Manon C.W. Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Leon M.G. Moons
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Tanya M. Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Jan Paul de Boer
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Wieke H.M. Verbeek
- Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | | | - Cecile P.M. Janus
- Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Eefke J. Petersen
- Department of Hematology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Judith M. Roesink
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | | | | | - Berthe M.P. Aleman
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Gerrit A. Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Flora E. van Leeuwen
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Petur Snaebjornsson
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Beatriz Carvalho
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Monique E. van Leerdam
- Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.,Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands.,Corresponding Author: Iris Lansdorp-Vogelaar, Dr. Molewaterplein 40, Rotterdam 3015 GD, the Netherlands. Phone: 311-0703-8454; E-mail:
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Tivey A, Church M, Rothwell D, Dive C, Cook N. Circulating tumour DNA - looking beyond the blood. Nat Rev Clin Oncol 2022; 19:600-612. [PMID: 35915225 PMCID: PMC9341152 DOI: 10.1038/s41571-022-00660-y] [Citation(s) in RCA: 168] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2022] [Indexed: 02/06/2023]
Abstract
Over the past decade, various liquid biopsy techniques have emerged as viable alternatives to the analysis of traditional tissue biopsy samples. Such surrogate 'biopsies' offer numerous advantages, including the relative ease of obtaining serial samples and overcoming the issues of interpreting one or more small tissue samples that might not reflect the entire tumour burden. To date, the majority of research in the area of liquid biopsies has focused on blood-based biomarkers, predominantly using plasma-derived circulating tumour DNA (ctDNA). However, ctDNA can also be obtained from various non-blood sources and these might offer unique advantages over plasma ctDNA. In this Review, we discuss advances in the analysis of ctDNA from non-blood sources, focusing on urine, cerebrospinal fluid, and pleural or peritoneal fluid, but also consider other sources of ctDNA. We discuss how these alternative sources can have a distinct yet complementary role to that of blood ctDNA analysis and consider various technical aspects of non-blood ctDNA assay development. We also reflect on the settings in which non-blood ctDNA can offer distinct advantages over plasma ctDNA and explore some of the challenges associated with translating these alternative assays from academia into clinical use.
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Affiliation(s)
- Ann Tivey
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
- The Christie NHS Foundation Trust, Manchester, UK
| | - Matt Church
- The Christie NHS Foundation Trust, Manchester, UK
| | - Dominic Rothwell
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
- Cancer Research UK Manchester Institute Cancer Biomarker Centre, The University of Manchester, Manchester, UK
| | - Caroline Dive
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
- Cancer Research UK Manchester Institute Cancer Biomarker Centre, The University of Manchester, Manchester, UK
| | - Natalie Cook
- Division of Cancer Sciences, The University of Manchester, Manchester, UK.
- The Christie NHS Foundation Trust, Manchester, UK.
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He SY, Li YC, Wang Y, Peng HL, Zhou CL, Zhang CM, Chen SL, Yin JF, Lin M. Fecal gene detection based on next generation sequencing for colorectal cancer diagnosis. World J Gastroenterol 2022; 28:2920-2936. [PMID: 35978873 PMCID: PMC9280739 DOI: 10.3748/wjg.v28.i25.2920] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 03/18/2022] [Accepted: 05/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common malignancies worldwide. Given its insidious onset, the condition often already progresses to advanced stage when symptoms occur. Thus, early diagnosis is of great significance for timely clinical intervention, efficacy enhancement, and prognostic improvement. Featuring high throughput, fastness, and rich information, next generation sequencing (NGS) can greatly shorten the detection time, which is a widely used detection technique at present. AIM To screen specific genes or gene combinations in fecal DNA that are suitable for diagnosis and prognostic prediction of CRC, and to establish a technological platform for CRC screening, diagnosis, and efficacy monitoring through fecal DNA detection. METHODS NGS was used to sequence the stool DNA of patients with CRC, which were then compared with the genetic testing results of the stool samples of normal controls and patients with benign intestinal disease, as well as the tumor tissues of CRC patients. Specific genes or gene combinations in fecal DNA suitable for diagnosis and prognostic prediction of CRC were screened, and their significances in diagnosing CRC and predicting patients' prognosis were comprehensively evaluated. RESULTS High mutation frequencies of TP53, APC, and KRAS were detected in the stools and tumor tissues of CRC patients prior to surgery. Contrastively, no pathogenic mutations of the above three genes were noted in the postoperative stools, the normal controls, or the benign intestinal disease group. This indicates that tumor-specific DNA was detectable in the preoperative stools of CRC patients. The preoperative fecal expression of tumor-associated genes can reflect the gene mutations in tumor tissues to some extent. Compared to the postoperative stools and the stools in the two control groups, the pathogenic mutation frequencies of TP53 and KRAS were significantly higher for the preoperative stools (χ 2 = 7.328, P < 0.05; χ 2 = 4.219, P < 0.05), suggesting that fecal TP53 and KRAS genes can be used for CRC screening, diagnosis, and prognostic prediction. No significant difference in the pathogenic mutation frequency of the APC gene was found from the postoperative stools or the two control groups (χ 2 = 0.878, P > 0.05), so further analysis with larger sample size is required. Among CRC patients, the pathogenic mutation sites of TP53 occurred in 16 of 27 preoperative stools, with a true positive rate of 59.26%, while the pathogenic mutation sites of KRAS occurred in 10 stools, with a true positive rate of 37.04%. The sensitivity and negative predictive values of the combined genetic testing of TP53 and KRAS were 66.67% (18/27) and 68.97%, respectively, both of which were higher than those of TP53 or KRAS mutation detection alone, suggesting that the combined genetic testing can improve the CRC detection rate. The mutation sites TP53 exon 4 A84G and EGFR exon 20 I821T (mutation start and stop positions were both 7579436 for the former, while 55249164 for the latter) were found in the preoperative stools and tumor tissues. These "undetected" mutation sites may be new types of mutations occurring during the CRC carcinogenesis and progression, which needs to be confirmed through further research. Some mutations of "unknown clinical significance" were found in such genes as TP53, PTEN, KRAS, BRAF, AKT1, and PIK3CA, whose clinical values is worthy of further exploration. CONCLUSION NGS-based fecal genetic testing can be used as a complementary technique for the CRC diagnosis. Fecal TP53 and KRAS can be used as specific genes for the screening, diagnosis, prognostic prediction, and recurrence monitoring of CRC. Moreover, the combined testing of TP53 and KRAS genes can improve the CRC detection rate.
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Affiliation(s)
- Si-Yu He
- Department of Clinical Laboratory, Taizhou People's Hospital (Postgraduate Training Base of Dalian Medical University), Taizhou 225300, Jiangsu Province, China
- Department of Clinical Laboratory, The First People's Hospital of Tianmen City, Tianmen 431700, Hubei Province, China
| | - Ying-Chun Li
- Department of General Surgery, Taizhou People's Hospital (Postgraduate Training Base of Dalian Medical University), Taizhou 225300, Jiangsu Province, China
| | - Yong Wang
- Department of General Surgery, Taizhou People's Hospital (Postgraduate Training Base of Dalian Medical University), Taizhou 225300, Jiangsu Province, China
| | - Hai-Lin Peng
- Department of Clinical Laboratory, Taizhou People's Hospital (Postgraduate Training Base of Dalian Medical University), Taizhou 225300, Jiangsu Province, China
| | - Cheng-Lin Zhou
- Department of Clinical Laboratory, Taizhou People's Hospital (Postgraduate Training Base of Dalian Medical University), Taizhou 225300, Jiangsu Province, China
| | - Chuan-Meng Zhang
- Central Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou 225300, Jiangsu Province, China
| | - Sheng-Lan Chen
- Department of Laboratory, Taizhou Genewill Medical Laboratory Company Limited, Taizhou 225300, Jiangsu Province, China
| | - Jian-Feng Yin
- Department of Laboratory, Jiangsu CoWin Biotech Co., Ltd., Taizhou 225300, Jiangsu Province, China
| | - Mei Lin
- Department of Clinical Laboratory, Taizhou People's Hospital (Postgraduate Training Base of Dalian Medical University), Taizhou 225300, Jiangsu Province, China
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10
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Feng Z, Oberije CJG, van de Wetering AJP, Koch A, Wouters KAD, Vaes N, Masclee AAM, Carvalho B, Meijer GA, Zeegers MP, Herman JG, Melotte V, van Engeland M, Smits KM. Lessons From a Systematic Literature Search on Diagnostic DNA Methylation Biomarkers for Colorectal Cancer: How to Increase Research Value and Decrease Research Waste? Clin Transl Gastroenterol 2022; 13:e00499. [PMID: 35584320 PMCID: PMC9236597 DOI: 10.14309/ctg.0000000000000499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 04/22/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES To improve colorectal cancer (CRC) survival and lower incidence rates, colonoscopy and/or fecal immunochemical test screening are widely implemented. Although candidate DNA methylation biomarkers have been published to improve or complement the fecal immunochemical test, clinical translation is limited. We describe technical and methodological problems encountered after a systematic literature search and provide recommendations to increase (clinical) value and decrease research waste in biomarker research. In addition, we present current evidence for diagnostic CRC DNA methylation biomarkers. METHODS A systematic literature search identified 331 diagnostic DNA methylation marker studies published before November 2020 in PubMed, EMBASE, Cochrane Library, and Google Scholar. For 136 bodily fluid studies, extended data extraction was performed. STARD criteria and level of evidence were registered to assess reporting quality and strength for clinical translation. RESULTS Our systematic literature search revealed multiple issues that hamper the development of DNA methylation biomarkers for CRC diagnosis, including methodological and technical heterogeneity and lack of validation or clinical translation. For example, clinical translation and independent validation were limited, with 100 of 434 markers (23%) studied in bodily fluids, 3 of 434 markers (0.7%) translated into clinical tests, and independent validation for 92 of 411 tissue markers (22%) and 59 of 100 bodily fluids markers (59%). DISCUSSION This systematic literature search revealed that major requirements to develop clinically relevant diagnostic CRC DNA methylation markers are often lacking. To avoid the resulting research waste, clinical needs, intended biomarker use, and independent validation should be better considered before study design. In addition, improved reporting quality would facilitate meta-analysis, thereby increasing the level of evidence and enabling clinical translation.
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Affiliation(s)
- Zheng Feng
- Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands;
| | - Cary J. G. Oberije
- Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands;
- The D-Lab, Department of Precision Medicine, GROW—School for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, the Netherlands;
| | - Alouisa J. P. van de Wetering
- Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands;
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands;
| | - Alexander Koch
- Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands;
| | - Kim. A. D. Wouters
- Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands;
| | - Nathalie Vaes
- Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands;
| | - Ad A. M. Masclee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands;
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands;
| | - Beatriz Carvalho
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands;
| | - Gerrit A. Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands;
| | - Maurice P. Zeegers
- Department of Complex Genetics, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands;
- Department of Complex Genetics, CAPHRI – Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, the Netherlands;
| | - James G. Herman
- Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
| | - Veerle Melotte
- Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands;
- Department of Clinical Genetics, Erasmus University Medical Center, University of Rotterdam, Rotterdam, the Netherlands;
| | - Manon van Engeland
- Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands;
| | - Kim M. Smits
- Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands;
- Division of Medical Oncology, Department of Internal Medicine, GROW – School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands.
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11
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Anderson JC, Robinson CM, Hisey WM, Edwards DK, Kneedler BL, Berger BM, Butterly LF. Colorectal Neoplasia Detection in Individuals With Positive Multitarget Stool DNA Tests: Data From the New Hampshire Colonoscopy Registry. J Clin Gastroenterol 2022; 56:419-425. [PMID: 33973962 DOI: 10.1097/mcg.0000000000001554] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 03/17/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND The US Preventive Services Task Force (USPSTF) includes multitarget stool DNA (mt-sDNA) testing as a colorectal cancer (CRC) screening option in average-risk individuals, but data on colonoscopy outcomes after positive mt-sDNA tests in community settings are needed. AIM The aim of this study was to investigate colonoscopy outcomes and quality following positive mt-sDNA in the population-based New Hampshire Colonoscopy Registry. METHODS We compared colonoscopy outcomes and quality between age-matched, sex-matched, and risk-matched patients from 30 endoscopy practices with and without a preceding positive mt-sDNA test. Main outcomes were colonoscopy findings of CRC, advanced noncancerous neoplasia, nonadvanced neoplasia, or normal examination. Quality measures included withdrawal time, bowel preparation quality, examination completion, and percentage of average-risk individuals with normal colonoscopies receiving a USPSTF-recommended 10 year rescreening interval. RESULTS Individuals with positive mt-sDNA tests (N=306, average age 67.0 y; 61.8% female) were significantly more likely than colonoscopy-only patients (N=918, 66.2 y; 61.8% female) to have CRC (1.3% vs. 0.4%) or advanced noncancerous neoplasia (27.1% vs. 8.2%) (P<0.0001). Neoplasia was found in 68.0% of patients having colonoscopy after a positive mt-sDNA test, (positive predictive value, was 68.0%), versus 42.3% of patients with colonoscopy only (P<0.0001). No significant differences in colonoscopy quality measures were observed between cohorts. CONCLUSIONS Colonoscopy after a positive mt-sDNA test was more frequently associated with CRC and colorectal neoplasia than colonoscopy alone. Positive mt-sDNA tests can enrich the proportion of colonoscopies with clinically relevant findings. Follow-up recommendations suggest that endoscopists do not inappropriately shorten rescreening intervals in mt-sDNA-positive patients with normal colonoscopy. These findings support the clinical utility of mt-sDNA for CRC screening in community practice.
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Affiliation(s)
| | - Christina M Robinson
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center
- NH Colonoscopy Registry, Lebanon, NH
| | | | | | | | | | - Lynn F Butterly
- Geisel School of Medicine at Dartmouth, Hanover
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center
- NH Colonoscopy Registry, Lebanon, NH
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12
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Beltrán-García J, Osca-Verdegal R, Mena-Mollá S, Seco-Cervera M, Peiró-Chova L, García-Giménez JL, Laurent-Puig P, Cervantes A. Translational epigenetics in precision medicine of colorectal cancer. EPIGENETICS IN PRECISION MEDICINE 2022:19-41. [DOI: 10.1016/b978-0-12-823008-4.00018-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Post-polypectomy colonoscopy surveillance: Can we improve the diagnostic yield? GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:474-487. [PMID: 34848307 DOI: 10.1016/j.gastrohep.2021.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/29/2021] [Accepted: 11/15/2021] [Indexed: 11/21/2022]
Abstract
Although adenomas and serrated polyps are the preneoplastic lesions of colorectal cancer, only few of them will eventually progress to cancer. This review provides a comprehensive overview of the present and future of post-polypectomy colonoscopy surveillance. Post-polypectomy surveillance guidelines have recently been updated and all share the aim towards more selective and less frequent surveillance. We have examined these current guidelines and compared the recommendations of each of them. To improve the diagnostic yield of post-polypectomy surveillance it is important to find predictors of metachronous polyps that better identify high-risk individuals of developing advanced neoplasia. For this reason, we have also conducted a literature review of the molecular biomarkers of metachronous advanced colorectal polyps. Finally, we have discussed future directions of post-polypectomy surveillance and identified possible strategies to improve the use of endoscopic resources with the COVID-19 pandemic.
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14
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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.
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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
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15
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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.
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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
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16
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Rademakers G, Massen M, Koch A, Draht MX, Buekers N, Wouters KAD, Vaes N, De Meyer T, Carvalho B, Meijer GA, Herman JG, Smits KM, van Engeland M, Melotte V. Identification of DNA methylation markers for early detection of CRC indicates a role for nervous system-related genes in CRC. Clin Epigenetics 2021; 13:80. [PMID: 33858496 PMCID: PMC8048074 DOI: 10.1186/s13148-021-01067-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 04/04/2021] [Indexed: 12/17/2022] Open
Abstract
Purpose Colonoscopy and the fecal immunochemical test (FIT) are currently the most widely used screening modalities for colorectal cancer (CRC), however, both with their own limitations. Here we aim to identify and validate stool-based DNA methylation markers for the early detection of CRC and investigate the biological pathways prone to DNA methylation. Methods DNA methylation marker discovery was performed using The Cancer Genome Atlas (TCGA) colon adenocarcinoma data set consisting of normal and primary colon adenocarcinoma tissue. The performance of the five best candidate markers and a previously identified marker, NDRG4, was evaluated on tissues and whole stool samples of healthy subjects and CRC patients using quantitative MSP assays. The results were compared and combined with FIT data. Finally, pathway and gene ontology enrichment analyses were performed using ToppFun, GOrilla and clusterProfiler. Results GDNF, HAND2, SLC35F3, SNAP91 and SORCS1 were ranked as the best performing markers. Gene combinations of all five markers, NDRG4 and FIT were evaluated to establish the biomarker panel with the highest diagnostic potential, resulting in the identification of GDNF/SNAP91/NDRG4/FIT as the best performing marker panel. Pathway and gene ontology enrichment analyses revealed that genes associated with the nervous system were enriched in the set of best performing CRC-specific biomarkers. Conclusion In silico discovery analysis using TCGA-derived data yielded a novel DNA-methylation-based assay for the early detection of CRC, potentially improving current screening modalities. Additionally, nervous system-related pathways were enriched in the identified genes, indicating an epigenetic regulation of neuronal genes in CRC. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-021-01067-9.
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Affiliation(s)
- Glenn Rademakers
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
| | - Maartje Massen
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
| | - Alexander Koch
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
| | - Muriel X Draht
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
| | - Nikkie Buekers
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
| | - Kim A D Wouters
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
| | - Nathalie Vaes
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
| | - Tim De Meyer
- Department of Data Analysis and Mathematical Modelling, Ghent University, Ghent, Belgium
| | - Beatriz Carvalho
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Gerrit A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - James G Herman
- The Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
| | - Kim M Smits
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
| | - Manon van Engeland
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
| | - Veerle Melotte
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. .,Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
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17
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Jin H, Wang J, Zhang C. The Value of Multi-targeted Fecal DNA Methylation Detection for Colorectal Cancer Screening in a Chinese Population. J Cancer 2021; 12:1644-1650. [PMID: 33613751 PMCID: PMC7890319 DOI: 10.7150/jca.47214] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 12/11/2020] [Indexed: 12/23/2022] Open
Abstract
Objective: To design a multi-targeted fecal DNA methylation kit and explore its value for clinical application among Chinese people. Methods: Based on previous research, a multi-targeted fecal DNA methylation detection kit, using four genes, was designed and clinically validated. Results: The methylation PCR from 279 patients met the requirements for the detection criteria. When all four molecular markers were negative, the negative predictive value (NPV) for colorectal cancer was 100% and the NPV for colorectal polyps was 84.21%. When one molecular marker was positive, the sensitivity (Se) for colorectal cancer was 76.4%-90.3%, the specificity (Sp) was 68.3-93.4%, and the positive predictive value (PPV) for colorectal cancer was 54.5-85.5%, and the NPV was 87.0-95.0%. For colorectal polyps, the Se was 41.0-52.5%, Sp 69.5-91.5%, and the PPV for colorectal polyps was 41.0-70.3%, the NPV was 75.2-79.3%. When two molecular markers were positive, the Se for colorectal cancer was 52.6-73.7%, the Sp was 93.2-98.3%, the PPV for colorectal cancer was 84.6-96.2%, the NPV was 76.0-85.3%. For colorectal polyps, the Se was 25.9-40.7%, Sp was 93.2-98.3%, PPV for screening of colorectal polyps was 63.6-90.0%, and the NPV was 73.3-78.1%. When three molecular markers were positive, the Se for colorectal cancer was 31.6-52.6%, the Sp was 98.3-100.0%, the PPV for colorectal cancer was 94.4-100.0%, the NPV was 73.4-76.6%. For colorectal polyps, the Se was 14.8-25.9%, and Sp was 98.3-100.0%, the PPV for colorectal polyps was 85.7-100.0%, the NPV was 72.0-74.7%. When four molecular markers were positive, the Se for colorectal cancer was 31.6%, the Sp was 100.0%, and the colorectal cancer PPV was 100.0% and the NPV was 69.4%. For polyps, the Se was 14.8%, Sp was 100.0%, and PPV was 100.0% and the NPV was 72.0%. Conclusion: The multi-targeted fecal DNA methylation detection kit for colorectal cancer and polyps had the sensitivity and specificity to meet the requirements for screening of colorectal tumors, which is easy to operate, has stable results and important clinical value. Among the four molecular markers studied, when one marker was positive for DNA methylation, colonoscopy was required; as the number of positive methylation markers increased, the specificity for the diagnosis gradually increased as well.
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Affiliation(s)
- Heiying Jin
- Department of colorectal surgery, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, 23 Nanhu Road, Nanjing 210017, China
| | - Jun Wang
- Department of colorectal surgery, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, 23 Nanhu Road, Nanjing 210017, China
| | - Chunxia Zhang
- Department of colorectal surgery, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, 23 Nanhu Road, Nanjing 210017, China
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18
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Galardi F, De Luca F, Romagnoli D, Biagioni C, Moretti E, Biganzoli L, Di Leo A, Migliaccio I, Malorni L, Benelli M. Cell-Free DNA-Methylation-Based Methods and Applications in Oncology. Biomolecules 2020; 10:E1677. [PMID: 33334040 PMCID: PMC7765488 DOI: 10.3390/biom10121677] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/07/2020] [Accepted: 12/14/2020] [Indexed: 12/11/2022] Open
Abstract
Liquid biopsy based on cell-free DNA (cfDNA) enables non-invasive dynamic assessment of disease status in patients with cancer, both in the early and advanced settings. The analysis of DNA-methylation (DNAm) from cfDNA samples holds great promise due to the intrinsic characteristics of DNAm being more prevalent, pervasive, and cell- and tumor-type specific than genomics, for which established cfDNA assays already exist. Herein, we report on recent advances on experimental strategies for the analysis of DNAm in cfDNA samples. We describe the main steps of DNAm-based analysis workflows, including pre-analytics of cfDNA samples, DNA treatment, assays for DNAm evaluation, and methods for data analysis. We report on protocols, biomolecular techniques, and computational strategies enabling DNAm evaluation in the context of cfDNA analysis, along with practical considerations on input sample requirements and costs. We provide an overview on existing studies exploiting cell-free DNAm biomarkers for the detection and monitoring of cancer in early and advanced settings, for the evaluation of drug resistance, and for the identification of the cell-of-origin of tumors. Finally, we report on DNAm-based tests approved for clinical use and summarize their performance in the context of liquid biopsy.
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Affiliation(s)
- Francesca Galardi
- «Sandro Pitigliani» Translational Research Unit, Hospital of Prato, 59100 Prato, Italy; (F.G.); (F.D.L.); (I.M.); (L.M.)
| | - Francesca De Luca
- «Sandro Pitigliani» Translational Research Unit, Hospital of Prato, 59100 Prato, Italy; (F.G.); (F.D.L.); (I.M.); (L.M.)
| | - Dario Romagnoli
- Bioinformatics Unit, Hospital of Prato, 59100 Prato, Italy; (D.R.); (C.B.)
| | - Chiara Biagioni
- Bioinformatics Unit, Hospital of Prato, 59100 Prato, Italy; (D.R.); (C.B.)
- «Sandro Pitigliani» Medical Oncology Department, Hospital of Prato, 59100 Prato, Italy; (E.M.); (L.B.); (A.D.L.)
| | - Erica Moretti
- «Sandro Pitigliani» Medical Oncology Department, Hospital of Prato, 59100 Prato, Italy; (E.M.); (L.B.); (A.D.L.)
| | - Laura Biganzoli
- «Sandro Pitigliani» Medical Oncology Department, Hospital of Prato, 59100 Prato, Italy; (E.M.); (L.B.); (A.D.L.)
| | - Angelo Di Leo
- «Sandro Pitigliani» Medical Oncology Department, Hospital of Prato, 59100 Prato, Italy; (E.M.); (L.B.); (A.D.L.)
| | - Ilenia Migliaccio
- «Sandro Pitigliani» Translational Research Unit, Hospital of Prato, 59100 Prato, Italy; (F.G.); (F.D.L.); (I.M.); (L.M.)
| | - Luca Malorni
- «Sandro Pitigliani» Translational Research Unit, Hospital of Prato, 59100 Prato, Italy; (F.G.); (F.D.L.); (I.M.); (L.M.)
- «Sandro Pitigliani» Medical Oncology Department, Hospital of Prato, 59100 Prato, Italy; (E.M.); (L.B.); (A.D.L.)
| | - Matteo Benelli
- Bioinformatics Unit, Hospital of Prato, 59100 Prato, Italy; (D.R.); (C.B.)
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Liquid biopsy as a perioperative biomarker of digestive tract cancers: review of the literature. Surg Today 2020; 51:849-861. [PMID: 32979121 DOI: 10.1007/s00595-020-02148-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 08/10/2020] [Indexed: 10/23/2022]
Abstract
Tissue biopsies are the gold-standard for investigating the molecular characterization of tumors. However, a "solid" biopsy is an invasive procedure that cannot capture real-time tumor dynamics and may yield inaccurate information because of intratumoral heterogeneity. In this review, we summarize the current state of knowledge about surgical treatment-associated "liquid" biopsy for patients with digestive organ tumors. A liquid biopsy is a technique involving the sampling and testing of non-solid biological materials, including blood, urine, saliva, and ascites. Previous studies have reported the potential value of blood-based biomarkers, circulating tumor cells, and cell-free nucleic acids as facilitators of cancer treatment. The applications of a liquid biopsy in a cancer treatment setting include screening and early diagnosis, prognostication, and outcome and recurrence monitoring of cancer. This technique has also been suggested as a useful tool in personalized medicine. The transition to precision medicine is still in its early stages. Soon, however, liquid biopsy is likely to form the basis of patient selection for molecular targeted therapies, predictions regarding chemotherapy sensitivity, and real-time evaluations of therapeutic effects.
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20
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Tepus M, Yau TO. Non-Invasive Colorectal Cancer Screening: An Overview. Gastrointest Tumors 2020; 7:62-73. [PMID: 32903904 PMCID: PMC7445682 DOI: 10.1159/000507701] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/30/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) follows a protracted stepwise progression, from benign adenomas to malignant adenocarcinomas. If detected early, 90% of deaths are preventable. However, CRC is asymptomatic in its early-stage and arises sporadically within the population. Therefore, CRC screening is a public health priority. SUMMARY Faecal immunochemical test (FIT) is gradually replacing guaiac faecal occult blood test and is now the most commonly used screening tool for CRC screening program globally. However, FIT is still limited by the haemoglobin degradation and the intermittent bleeding patterns, so that one in four CRC cases are still diagnosed in a late stage, leading to poor prognosis. A multi-target stool DNA test (Cologuard, a combination of NDRG4 and BMP3 DNA methylation, KRAS mutations, and haemoglobin) and a plasma SEPT9 DNA methylation test (Epi proColon) are non-invasive tools also approved by the US FDA, but those screening approaches are not cost-effective, and the detection accuracies remain unsatisfactory. In addition to the approved tests, faecal-/blood-based microRNA and CRC-related gut microbiome screening markers are under development, with work ongoing to find the best combination of molecular biomarkers which maximise the screening sensitivity and specificity. KEY MESSAGE Maximising the detection accuracy with a cost-effective approach for non-invasive CRC screening is urgently needed to further reduce the incidence of CRC and associated mortality rates.
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Affiliation(s)
| | - Tung On Yau
- John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom
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21
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Hamarneh Z, Symonds EL, Kholmurodova F, Cock C. Older age, symptoms, or anemia: Which factors increase colorectal cancer risk with a positive fecal immunochemical test? J Gastroenterol Hepatol 2020; 35:1002-1008. [PMID: 31606908 DOI: 10.1111/jgh.14888] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 09/30/2019] [Accepted: 10/02/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM Fecal immunochemical tests (FIT) are used to screen asymptomatic individuals aged 50-74 years for colorectal cancer (CRC) within the Australian screening program. Gastrointestinal symptoms or iron deficiency anemia (IDA) may also drive primary care physicians to request a FIT. This study aimed to examine factors that may increase neoplasia risk associated with a positive FIT, specifically age, gastrointestinal symptoms, or IDA. METHODS A retrospective audit was performed on colonoscopies performed in a single hospital in South Australia for a positive FIT (from all referral sources) between 2014 and 2017. Patients aged < 50 years, or who had a colonoscopy in the preceding 5 years, were excluded. A subgroup (n = 198) was evaluated to assess whether age ≥ 75 years, symptoms, or IDA, as well as other demographics, comorbidities, and medications, were associated with risk of neoplasia. Features found to be associated with risk for CRC or high-risk adenoma were examined in the entire cohort using multivariate analysis. RESULTS Colonoscopies (750/4221, 17.8%) were completed in patients ≥ 50 years for a positive FIT. Of these, 7.6% (n = 57) also had gastrointestinal symptoms, 5.5% (n = 41) IDA, and 13.1% (n = 98) were ≥ 75 years. At colonoscopy, 2.8% (n = 21) were diagnosed with CRC and 23.2% (n = 174) with high-risk adenoma. CRC was more prevalent in ≥ 75 years compared with 50-74 years (7.1% vs 2.1%, P = 0.005), and associated with symptoms (15.8% vs 1.7%, P < 0.001), and IDA (14.6% vs 2.1%, P < 0.001). Multivariate analysis showed that IDA (odds ratio 7.68, P < 0.001) and symptoms (odds ratio 10.37, P < 0.001), but not age, were independent risk factors for CRC. CONCLUSION The presence of gastrointestinal symptoms or IDA, independent of age, is associated with an increased risk for CRC following a positive FIT.
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Affiliation(s)
- Zaki Hamarneh
- Department of Gastroenterology and Hepatology, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Erin L Symonds
- Bowel Health Service, Flinders Medical Centre, Adelaide, South Australia, Australia.,Flinders Centre for Innovation in Cancer, Adelaide, South Australia, Australia
| | - Feruza Kholmurodova
- Flinders Centre for Innovation in Cancer, Adelaide, South Australia, Australia.,Flinders Centre for Epidemiology and Biostatistics, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Charles Cock
- Department of Gastroenterology and Hepatology, Flinders Medical Centre, Adelaide, South Australia, Australia
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22
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Jung G, Hernández-Illán E, Moreira L, Balaguer F, Goel A. Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol 2020; 17:111-130. [PMID: 31900466 PMCID: PMC7228650 DOI: 10.1038/s41575-019-0230-y] [Citation(s) in RCA: 504] [Impact Index Per Article: 100.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/16/2019] [Indexed: 12/24/2022]
Abstract
Colorectal cancer (CRC), a leading cause of cancer-related death worldwide, evolves as a result of the stepwise accumulation of a series of genetic and epigenetic alterations in the normal colonic epithelium, leading to the development of colorectal adenomas and invasive adenocarcinomas. Although genetic alterations have a major role in a subset of CRCs, the pathophysiological contribution of epigenetic aberrations in this malignancy has attracted considerable attention. Data from the past couple of decades has unequivocally illustrated that epigenetic marks are important molecular hallmarks of cancer, as they occur very early in disease pathogenesis, involve virtually all key cancer-associated pathways and, most importantly, can be exploited as clinically relevant disease biomarkers for diagnosis, prognostication and prediction of treatment response. In this Review, we summarize the current knowledge on the best-studied epigenetic modifications in CRC, including DNA methylation and histone modifications, as well as the role of non-coding RNAs as epigenetic regulators. We focus on the emerging potential for the bench-to-bedside translation of some of these epigenetic alterations into clinical practice and discuss the burgeoning evidence supporting the potential of emerging epigenetic therapies in CRC as we usher in the era of precision medicine.
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Affiliation(s)
- Gerhard Jung
- Gastroenterology Department, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Eva Hernández-Illán
- Gastroenterology Department, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Leticia Moreira
- Gastroenterology Department, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
| | - Ajay Goel
- Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
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23
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Matsuoka T, Yashiro M. Precision medicine for gastrointestinal cancer: Recent progress and future perspective. World J Gastrointest Oncol 2020; 12:1-20. [PMID: 31966910 PMCID: PMC6960076 DOI: 10.4251/wjgo.v12.i1.1] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 10/12/2019] [Accepted: 11/04/2019] [Indexed: 02/05/2023] Open
Abstract
Gastrointestinal (GI) cancer has a high tumor incidence and mortality rate worldwide. Despite significant improvements in radiotherapy, chemotherapy, and targeted therapy for GI cancer over the last decade, GI cancer is characterized by high recurrence rates and a dismal prognosis. There is an urgent need for new diagnostic and therapeutic approaches. Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer. Here we review the application and status of precision medicine in GI cancer. Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy. With the introduction of gene panels including next-generation sequencing, it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer. Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors, novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs. These progressions will make it feasible to incorporate clinical, genome-based, and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.
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Affiliation(s)
- Tasuku Matsuoka
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
| | - Masakazu Yashiro
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
- Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
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24
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Diagnostic Accuracy of Stool Tests for Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors. J Clin Med 2020; 9:jcm9010190. [PMID: 31936745 PMCID: PMC7019558 DOI: 10.3390/jcm9010190] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 01/06/2020] [Accepted: 01/08/2020] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Hodgkin lymphoma (HL) survivors have an increased colorectal cancer (CRC) risk. Diagnostic accuracy of quantitative fecal immunochemical testing (FIT, OC Sensor) and/or a multi-target stool DNA test (mt-sDNA, Cologuard®) for advanced neoplasia (AN) was evaluated. METHODS 101 HL survivors underwent a surveillance colonoscopy and were asked to perform two stool tests (FIT and mt-sDNA). Advanced adenoma (AA), advanced serrated lesion (ASL), and AN (AA, ASL, CRC) were evaluated. Sensitivity, specificity, and area under the curve (AUC) for AN were calculated for different FIT cut-offs and mt-sDNA with colonoscopy as reference. RESULTS FIT and mt-sDNA were analyzed in 73 (72%) and 82 (81%) participants, respectively. AN was detected in 19 (26%) and 22 (27%), respectively. AN sensitivities for FIT cut-off of 10 ug Hb/g feces (FIT10) and mt-sDNA were 37% (95% confidence interval (CI): 16-62) and 68% (95% CI: 45-86), with corresponding specificities of 91% (95% CI: 80-97) and 70% (95% CI: 57-86), respectively. AUC for FIT was 0.68 (95% CI: 0.54-0.82) and for mt-sDNA 0.76 (95% CI: 0.63-0.89). CONCLUSIONS In HL survivors, mt-sDNA showed highest sensitivity but with relatively low specificity for AN. Cost-effectiveness analyses is necessary to determine the optimal surveillance strategy.
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25
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Cross AJ, Wooldrage K, Robbins EC, Kralj-Hans I, MacRae E, Piggott C, Stenson I, Prendergast A, Patel B, Pack K, Howe R, Swart N, Snowball J, Duffy SW, Morris S, von Wagner C, Halloran SP, Atkin WS. Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study. Gut 2019; 68:1642-1652. [PMID: 30538097 PMCID: PMC6709777 DOI: 10.1136/gutjnl-2018-317297] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 11/21/2018] [Accepted: 11/25/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER ISRCTN18040196; Results.
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Affiliation(s)
- Amanda J Cross
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Kate Wooldrage
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Emma C Robbins
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Ines Kralj-Hans
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Eilidh MacRae
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Carolyn Piggott
- Bowel Cancer Screening Programme Southern Hub, Guildford, UK
| | - Iain Stenson
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Aaron Prendergast
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Bhavita Patel
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Kevin Pack
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Rosemary Howe
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Nicholas Swart
- Department of Applied Health Research, University College London, London, UK
| | - Julia Snowball
- Bowel Cancer Screening Programme Southern Hub, Guildford, UK
| | - Stephen W Duffy
- Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University, London, UK
| | - Stephen Morris
- Department of Applied Health Research, University College London, London, UK
| | - Christian von Wagner
- Research Department of Behavioural Science and Health, University College London, London, UK
| | - Stephen P Halloran
- Bowel Cancer Screening Programme Southern Hub, Guildford, UK
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Wendy S Atkin
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
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26
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Beltrán-García J, Osca-Verdegal R, Mena-Mollá S, García-Giménez JL. Epigenetic IVD Tests for Personalized Precision Medicine in Cancer. Front Genet 2019; 10:621. [PMID: 31316555 PMCID: PMC6611494 DOI: 10.3389/fgene.2019.00621] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 06/13/2019] [Indexed: 12/12/2022] Open
Abstract
Epigenetic alterations play a key role in the initiation and progression of cancer. Therefore, it is possible to use epigenetic marks as biomarkers for predictive and precision medicine in cancer. Precision medicine is poised to impact clinical practice, patients, and healthcare systems. The objective of this review is to provide an overview of the epigenetic testing landscape in cancer by examining commercially available epigenetic-based in vitro diagnostic tests for colon, breast, cervical, glioblastoma, lung cancers, and for cancers of unknown origin. We compile current commercial epigenetic tests based on epigenetic biomarkers (i.e., DNA methylation, miRNAs, and histones) that can actually be implemented into clinical practice.
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Affiliation(s)
- Jesús Beltrán-García
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain.,INCLIVA Biomedical Research Institute, Valencia, Spain.,Department of Physiology, School of Medicine and Dentistry, Universitat de València (UV), Valencia, Spain
| | - Rebeca Osca-Verdegal
- INCLIVA Biomedical Research Institute, Valencia, Spain.,Department of Physiology, School of Medicine and Dentistry, Universitat de València (UV), Valencia, Spain
| | - Salvador Mena-Mollá
- Department of Physiology, School of Medicine and Dentistry, Universitat de València (UV), Valencia, Spain.,EpiDisease S.L. Spin-Off of CIBERER (ISCIII), Valencia, Spain
| | - José Luis García-Giménez
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain.,INCLIVA Biomedical Research Institute, Valencia, Spain.,Department of Physiology, School of Medicine and Dentistry, Universitat de València (UV), Valencia, Spain.,EpiDisease S.L. Spin-Off of CIBERER (ISCIII), Valencia, Spain
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27
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Gambhir SS, Shankar LK, Rosenthal E, Warram JM, Ghesani M, Hope TA, Jacobs PM, Jacobson GB, Wilson T, Siegel BA. Proceedings: Pathways for Successful Translation of New Imaging Agents and Modalities-Phase III Studies. J Nucl Med 2019; 60:736-744. [PMID: 30850482 DOI: 10.2967/jnumed.118.219824] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 11/28/2018] [Indexed: 12/19/2022] Open
Affiliation(s)
- Sanjiv S Gambhir
- Departments of Radiology, Bioengineering, and Materials Science and Engineering, Molecular Imaging Program, Stanford University, Stanford, California
| | - Lalitha K Shankar
- Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland
| | - Eben Rosenthal
- Department of Otolaryngology, Stanford University, Stanford, California
| | - Jason M Warram
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Munir Ghesani
- Department of Radiology, New York University, New York, New York
| | - Thomas A Hope
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California
| | - Paula M Jacobs
- Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland
| | - Gunilla B Jacobson
- Department of Radiology, Molecular Imaging Program, Stanford University, Stanford, California
| | - Terri Wilson
- Blue Earth Diagnostics, Inc., Burlington, Massachusetts; and
| | - Barry A Siegel
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
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28
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Atkin W, Cross AJ, Kralj-Hans I, MacRae E, Piggott C, Pearson S, Wooldrage K, Brown J, Lucas F, Prendergast A, Marchevsky N, Patel B, Pack K, Howe R, Skrobanski H, Kerrison R, Swart N, Snowball J, Duffy SW, Morris S, von Wagner C, Halloran S. Faecal immunochemical tests versus colonoscopy for post-polypectomy surveillance: an accuracy, acceptability and economic study. Health Technol Assess 2019; 23:1-84. [PMID: 30618357 PMCID: PMC6340104 DOI: 10.3310/hta23010] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In the UK, patients with one or two adenomas, of which at least one is ≥ 10 mm in size, or three or four small adenomas, are deemed to be at intermediate risk of colorectal cancer (CRC) and referred for surveillance colonoscopy 3 years post polypectomy. However, colonoscopy is costly, can cause discomfort and carries a small risk of complications. OBJECTIVES To determine whether or not annual faecal immunochemical tests (FITs) are effective, acceptable and cost saving compared with colonoscopy surveillance for detecting CRC and advanced adenomas (AAs). DESIGN Diagnostic accuracy study with health psychology assessment and economic evaluation. SETTING Participants were recruited from 30 January 2012 to 30 December 2013 within the Bowel Cancer Screening Programme in England. PARTICIPANTS Men and women, aged 60-72 years, deemed to be at intermediate risk of CRC following adenoma removal after a positive guaiac faecal occult blood test were invited to participate. Invitees who consented and returned an analysable FIT were included. INTERVENTION We offered participants quantitative FITs at 1, 2 and 3 years post polypectomy. Participants testing positive with any FIT were referred for colonoscopy and not offered further FITs. Participants testing negative were offered colonoscopy at 3 years post polypectomy. Acceptibility of FIT was assessed using discussion groups, questionnaires and interviews. MAIN OUTCOME MEASURES The primary outcome was 3-year sensitivity of an annual FIT versus colonoscopy at 3 years for detecting advanced colorectal neoplasia (ACN) (CRC and/or AA). Secondary outcomes included participants' surveillance preferences, and the incremental costs and cost-effectiveness of FIT versus colonoscopy surveillance. RESULTS Of 8008 invitees, 5946 (74.3%) consented and returned a round 1 FIT. FIT uptake in rounds 2 and 3 was 97.2% and 96.9%, respectively. With a threshold of 40 µg of haemoglobin (Hb)/g faeces (hereafter referred to as µg/g), positivity was 5.8% in round 1, declining to 4.1% in round 3. Over three rounds, 69.2% (18/26) of participants with CRC, 34.3% (152/443) with AAs and 35.6% (165/463) with ACN tested positive at 40 µg/g. Sensitivity for CRC and AAs increased, whereas specificity decreased, with lower thresholds and multiple rounds. At 40 µg/g, sensitivity and specificity of the first FIT for CRC were 30.8% and 93.9%, respectively. The programme sensitivity and specificity of three rounds at 10 µg/g were 84.6% and 70.8%, respectively. Participants' preferred surveillance strategy was 3-yearly colonoscopy plus annual FITs (57.9%), followed by annual FITs with colonoscopy in positive cases (31.5%). FIT with colonoscopy in positive cases was cheaper than 3-yearly colonoscopy (£2,633,382), varying from £485,236 (40 µg/g) to £956,602 (10 µg/g). Over 3 years, FIT surveillance could miss 291 AAs and eight CRCs using a threshold of 40 µg/g, or 189 AAs and four CRCs using a threshold of 10 µg/g. CONCLUSIONS Annual low-threshold FIT with colonoscopy in positive cases achieved high sensitivity for CRC and would be cost saving compared with 3-yearly colonoscopy. However, at higher thresholds, this strategy could miss 15-30% of CRCs and 40-70% of AAs. Most participants preferred annual FITs plus 3-yearly colonoscopy. Further research is needed to define a clear role for FITs in surveillance. FUTURE WORK Evaluate the impact of ACN missed by FITs on quality-adjusted life-years. TRIAL REGISTRATION Current Controlled Trials ISRCTN18040196. FUNDING National Institute for Health Research (NIHR) Health Technology Assessment programme, NIHR Imperial Biomedical Research Centre and the Bobby Moore Fund for Cancer Research UK. MAST Group Ltd provided FIT kits.
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Affiliation(s)
- Wendy Atkin
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Amanda J Cross
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Ines Kralj-Hans
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Eilidh MacRae
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Carolyn Piggott
- Bowel Cancer Screening Programme Southern Hub, Guildford, UK
| | - Sheena Pearson
- Bowel Cancer Screening Programme Southern Hub, Guildford, UK
| | - Kate Wooldrage
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Jeremy Brown
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Fiona Lucas
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Aaron Prendergast
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Natalie Marchevsky
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Bhavita Patel
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Kevin Pack
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Rosemary Howe
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Hanna Skrobanski
- Research Department of Behavioural Science and Health, University College London, London, UK
| | - Robert Kerrison
- Research Department of Behavioural Science and Health, University College London, London, UK
| | - Nicholas Swart
- Department of Applied Health Research, University College London, London, UK
| | - Julia Snowball
- Bowel Cancer Screening Programme Southern Hub, Guildford, UK
| | - Stephen W Duffy
- Centre for Cancer Prevention, Wolfson Institute of Preventative Medicine, Queen Mary University, London, UK
| | - Stephen Morris
- Department of Applied Health Research, University College London, London, UK
| | - Christian von Wagner
- Research Department of Behavioural Science and Health, University College London, London, UK
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29
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Vedeld HM, Goel A, Lind GE. Epigenetic biomarkers in gastrointestinal cancers: The current state and clinical perspectives. Semin Cancer Biol 2018; 51:36-49. [PMID: 29253542 PMCID: PMC7286571 DOI: 10.1016/j.semcancer.2017.12.004] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 11/17/2017] [Accepted: 12/12/2017] [Indexed: 02/07/2023]
Abstract
Each year, almost 4.1 million people are diagnosed with gastrointestinal (GI) cancers. Due to late detection of this disease, the mortality is high, causing approximately 3 million cancer-related deaths annually, worldwide. Although the incidence and survival differs according to organ site, earlier detection and improved prognostication have the potential to reduce overall mortality burden from these cancers. Epigenetic changes, including aberrant promoter DNA methylation, are common events in both cancer initiation and progression. Furthermore, such changes may be identified non-invasively with the use of PCR based methods, in bodily fluids of cancer patients. These features make aberrant DNA methylation a promising substrate for the development of disease biomarkers for early detection, prognosis and for predicting response to therapy. In this article, we will provide an update and current clinical perspectives for DNA methylation alterations in patients with colorectal, gastric, pancreatic, liver and esophageal cancers, and discuss their potential role as cancer biomarkers.
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Affiliation(s)
- Hege Marie Vedeld
- Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Ajay Goel
- Center for Gastrointestinal Research, and Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
| | - Guro E Lind
- Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
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30
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Roberts BS, Hardigan AA, Moore DE, Ramaker RC, Jones AL, Fitz-Gerald MB, Cooper GM, Wilcox CM, Kimberly RP, Myers RM. Discovery and Validation of Circulating Biomarkers of Colorectal Adenoma by High-Depth Small RNA Sequencing. Clin Cancer Res 2018; 24:2092-2099. [PMID: 29490987 PMCID: PMC5932113 DOI: 10.1158/1078-0432.ccr-17-1960] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 01/02/2018] [Accepted: 02/21/2018] [Indexed: 12/18/2022]
Abstract
Purpose: Colorectal cancer is the third most common cancer worldwide, causing approximately 700,000 deaths each year. The majority of colorectal cancers begin as adenomas. Definitive screening for colorectal adenomas is currently accomplished through colonoscopy but, owing largely to costs and invasiveness, is typically limited to patient groups at higher risk by virtue of age or family history. We sought to determine if blood-based small RNA markers could detect colorectal adenoma.Experimental Design: We applied high-depth small RNA sequencing to plasma from a large (n = 189) cohort of patients, balanced for age, sex, and ancestry. Our analytical methodology allowed for the detection of both microRNAs and other small RNA species. We replicated sequencing results by qPCR on plasma samples from an independent cohort (n = 140).Results: We found several small RNA species with significant associations to colorectal adenoma, including both microRNAs and non-microRNA small RNAs. These associations were robust to correction for patient covariates, including age. Among the adenoma-associated small RNAs, two, a miR-335-5p isoform and an un-annotated small RNA, were validated by qPCR in an independent cohort. A classifier trained on measures of these two RNAs in the discovery cohort yields an AUC of 0.755 (0.775 with age) for adenoma detection in the independent cohort. This classifier accurately detects adenomas in patients under 50 and is robust to sex or ancestry.Conclusions: Circulating small RNAs (including but not limited to miRNAs) discovered by sequencing and validated by qPCR identify patients with colorectal adenomas effectively. Clin Cancer Res; 24(9); 2092-9. ©2018 AACR.
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Affiliation(s)
- Brian S Roberts
- HudsonAlpha Institute for Biotechnology, Huntsville, Alabama
| | - Andrew A Hardigan
- HudsonAlpha Institute for Biotechnology, Huntsville, Alabama
- Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
| | - Dianna E Moore
- HudsonAlpha Institute for Biotechnology, Huntsville, Alabama
| | - Ryne C Ramaker
- HudsonAlpha Institute for Biotechnology, Huntsville, Alabama
- Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
| | - Angela L Jones
- HudsonAlpha Institute for Biotechnology, Huntsville, Alabama
| | - Meredith B Fitz-Gerald
- Center for Clinical and Translational Science, University of Alabama at Birmingham, Birmingham, Alabama
| | | | - C Mel Wilcox
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Robert P Kimberly
- Center for Clinical and Translational Science, University of Alabama at Birmingham, Birmingham, Alabama
- Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Richard M Myers
- HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
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31
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García-Giménez JL, Seco-Cervera M, Tollefsbol TO, Romá-Mateo C, Peiró-Chova L, Lapunzina P, Pallardó FV. Epigenetic biomarkers: Current strategies and future challenges for their use in the clinical laboratory. Crit Rev Clin Lab Sci 2017; 54:529-550. [PMID: 29226748 DOI: 10.1080/10408363.2017.1410520] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Epigenetic modifications and regulators represent potential molecular elements which control relevant physiological and pathological features, thereby contributing to the natural history of human disease. These epigenetic modulators can be employed as disease biomarkers, since they show several advantages and provide information about gene function, thus explaining differences among patient endophenotypes. In addition, epigenetic biomarkers can incorporate information regarding the effects of the environment and lifestyle on health and disease, and monitor the effect of applied therapies. Technologies used to analyze these epigenetic biomarkers are constantly improving, becoming much easier to use. Laboratory professionals can easily acquire experience and techniques are becoming more affordable. A high number of epigenetic biomarker candidates are being continuously proposed, making now the moment to adopt epigenetics in the clinical laboratory and convert epigenetic marks into reliable biomarkers. In this review, we describe some current promising epigenetic biomarkers and technologies being applied in clinical practice. Furthermore, we will discuss some laboratory strategies and kits to accelerate the adoption of epigenetic biomarkers into clinical routine. The likelihood is that over time, better markers will be identified and will likely be incorporated into future multi-target assays that might help to optimize its application in a clinical laboratory. This will improve cost-effectiveness, and consequently encourage the development of theragnosis and the application of precision medicine.
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Affiliation(s)
- José Luis García-Giménez
- a Center for Biomedical Network Research on Rare Diseases (CIBERER) , Institute of Health Carlos III , Valencia , Spain.,b INCLIVA Biomedical Research Institute , Valencia , Spain.,c Department Physiology, School of Medicine and Dentistry , Universitat de València (UV) , Valencia , Spain.,d Epigenetics Research Platform (CIBERER/UV/INCLIVA) , Valencia , Spain.,e EpiDisease S.L. Spin-Off of CIBERER (ISCIII) , Valencia , Spain
| | - Marta Seco-Cervera
- a Center for Biomedical Network Research on Rare Diseases (CIBERER) , Institute of Health Carlos III , Valencia , Spain.,b INCLIVA Biomedical Research Institute , Valencia , Spain.,c Department Physiology, School of Medicine and Dentistry , Universitat de València (UV) , Valencia , Spain
| | - Trygve O Tollefsbol
- f Department of Biology , University of Alabama at Birmingham , Birmingham , AL , USA
| | - Carlos Romá-Mateo
- a Center for Biomedical Network Research on Rare Diseases (CIBERER) , Institute of Health Carlos III , Valencia , Spain.,b INCLIVA Biomedical Research Institute , Valencia , Spain.,c Department Physiology, School of Medicine and Dentistry , Universitat de València (UV) , Valencia , Spain.,d Epigenetics Research Platform (CIBERER/UV/INCLIVA) , Valencia , Spain
| | - Lorena Peiró-Chova
- b INCLIVA Biomedical Research Institute , Valencia , Spain.,g INCLIVA Biobank , Valencia , Spain
| | - Pablo Lapunzina
- a Center for Biomedical Network Research on Rare Diseases (CIBERER) , Institute of Health Carlos III , Valencia , Spain.,h Institute of Medical and Molecular Genetics (INGEMM) , IdiPAZ, Hospital Universitario La Paz, Universidad Autónoma de Madrid , Madrid , Spain
| | - Federico V Pallardó
- a Center for Biomedical Network Research on Rare Diseases (CIBERER) , Institute of Health Carlos III , Valencia , Spain.,b INCLIVA Biomedical Research Institute , Valencia , Spain.,c Department Physiology, School of Medicine and Dentistry , Universitat de València (UV) , Valencia , Spain.,d Epigenetics Research Platform (CIBERER/UV/INCLIVA) , Valencia , Spain
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32
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Sweetser S, Ahlquist DA. Utility of the multitarget stool DNA test for detection of colorectal neoplasia. COLORECTAL CANCER 2017. [DOI: 10.2217/crc-2017-0010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Colorectal cancer (CRC) is an ideal target for screening because it and its precursor lesions are prevalent and can be detected at curable stages among asymptomatic persons. Different screening strategies have been shown to reduce CRC incidence and mortality; therefore, CRC screening is widely recommended. However, despite these demonstrated benefits, a large percentage of the population remains unscreened and efforts are underway in multiple countries to improve screening participation. The multitarget stool DNA test (MT-sDNA) is a new noninvasive option for CRC screening that is a now recommended as a primary CRC screening strategy in the updated guidelines by the US Preventive Services Task Force, American Cancer Society and National Comprehensive Cancer Network. MT-sDNA has high accuracy for detection of both CRC and polyps at the greatest risk of progression, and has potential to improve screening uptake and effectiveness. This review provides a summary of MT-sDNA performance for detection of colorectal neoplasia and a perspective on the value it adds to our screening tool kit.
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Affiliation(s)
- Seth Sweetser
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
| | - David A Ahlquist
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
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33
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Kormi SMA, Ardehkhani S, Kerachian MA. New insights into colorectal cancer screening and early detection tests. COLORECTAL CANCER 2017. [DOI: 10.2217/crc-2017-0007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Colorectal cancer (CRC) is a common cancer in both men and women worldwide. Creating a diagnostic panel is necessary for early diagnosis which could lead to a better long-term survival in cancer patients. Colonoscopy every 10 years, starting at age 50, is the preferred CRC screening test. Many studies have been worked on potential diagnostic biomarkers of CRC. In this article, we described the recent evolutions in the development of CRC noninvasive screening assays. Recently, a multifunctional fecal DNA test has been available commercially in the USA. A few other US FDA-approved tests like Epi proColon® (Epigenomics AG, Berlin, Germany) are also available now. Although a new marker class for fecal occult blood test, a novel biomarker based on fecal bacteria in CRC patients and circulating tumor cells are under investigation, there is still a strong need to do more research for CRC screening strategies.
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Affiliation(s)
- Seyed Mohammad Amin Kormi
- Cancer Genetics Research Unit, Reza Radiotherapy & Oncology Center, Mashhad, Iran
- Department of Biology, Faculty of Science, University of Zabol, Zabol, Iran
| | - Shima Ardehkhani
- Department of Applied Science & Technology, University of Payame Noor, Tehran, Iran
| | - Mohammad Amin Kerachian
- Cancer Genetics Research Unit, Reza Radiotherapy & Oncology Center, Mashhad, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Genetics, Faculty of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
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