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      Roles of Methylated DNA Biomarkers in Patients with Colorectal Cancer

      review-article
      Author(s): 1 , 2 , 2 , 1 ,
      Publication date (Electronic):
      Journal: Disease Markers
      Publisher: Hindawi

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          Abstract

          Colorectal cancer (CRC) is a leading cancer globally; therefore, early diagnosis and surveillance of this cancer are of paramount importance. Current methods of CRC diagnosis rely heavily on endoscopy or radiological imaging. Noninvasive tests including serum detection of the carcinoembryonic antigen (CEA) and faecal occult blood testing (FOBT) are associated with low sensitivity and specificity, especially at early stages. DNA methylation biomarkers have recently been found to have higher accuracy in CRC detection and enhanced prediction of prognosis and chemotherapy response. The most widely studied biomarker in CRC is methylated septin 9 (SEPT9), which is the only FDA-approved methylation-based biomarker for CRC. Apart from SEPT9, other methylated biomarkers including tachykinin-1 (TAC1), somatostatin (SST), and runt-related transcription factor 3 (RUNX3) have been shown to effectively detect CRC in a multitude of sample types. This review will discuss the performances of various methylated biomarkers used for CRC diagnosis and monitoring, when used alone or in combination.

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          CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer.

          Shuji Ogino, Katsuhiko Nosho, Gregory Kirkner … (2009)
          The CpG island methylator phenotype (CIMP), characterised by widespread promoter methylation, is associated with microsatellite instability (MSI) and BRAF mutation in colorectal cancer. The independent effect of CIMP, MSI and BRAF mutation on prognosis remains uncertain. Utilising 649 colon cancers (stage I-IV) in two independent cohort studies, we quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) as well as CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, and WRN by using MethyLight technology. We examined MSI, KRAS and BRAF status. Cox proportional hazard models computed hazard ratios (HRs) for colon cancer-specific and overall mortalities, adjusting for patient characteristics and tumoral molecular features. After adjustment for other predictors of patient survival, patients with CIMP-high cancers (126 (19%) tumours with >or=6/8 methylated CIMP-specific promoters) experienced a significantly low colon cancer-specific mortality (multivariate HR 0.44, 95% confidence interval (CI) 0.22 to 0.88), whereas the BRAF mutation was significantly associated with a high cancer-specific mortality (multivariate HR 1.97, 95% CI 1.13 to 3.42). A trend toward a low cancer-specific mortality was observed for MSI-high tumours (multivariate HR 0.70, 95% CI 0.36 to 1.37). In stratified analyses, CIMP-high tumours were associated with a significant reduction in colon cancer-specific mortality, regardless of both MSI and BRAF status. The relation between CIMP-high and lower mortality appeared to be consistent across all stages. KRAS mutation was unrelated to prognostic significance. CIMP-high appears to be an independent predictor of a low colon cancer-specific mortality, while BRAF mutation is associated with a high colon cancer-specific mortality.
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            Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use.

            R Lamerz, O. Topolcan, E Holinski-Feder … (2007)
            The aim of this article is to present updated guidelines for the use of serum, tissue and faecal markers in colorectal cancer (CRC). Lack of specificity and sensitivity preclude the use of all existing serum markers for the early detection of CRC. For patients with stage II or stage III CRC who may be candidates for either liver resection or systemic treatment should recurrence develop, CEA should be measured every 2-3 months for at least 3 years after diagnosis. Insufficient evidence exists to recommend routine use of tissue factors such as thymidylate synthase, microsatellite instability (MSI), p53, K-ras and deleted in colon cancer (DCC) for either determining prognosis or predicting response to therapy in patients with CRC. Microsatellite instability, however, may be used as a pre-screen for patients with suspected hereditary non-polyposis colorectal cancer. Faecal occult blood testing but not faecal DNA markers may be used to screen asymptomatic subjects 50 years or older for early CRC.
            Article 0 comments Cited 117 times – based on 0 reviews     Review now
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              Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer

              Federica Di Nicolantonio, Andrea Sartore-Bianchi, Alberto Bardelli … (2017)
              Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies. Our objective was to identify cancer-specific methylated biomarkers which could be measured longitudinally in cfDNA (liquid biopsy) to monitor therapeutic outcome in patients with metastatic CRC (mCRC).
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                Author and article information

                Contributors
                Wai K. Leung:
                ORCID: http://orcid.org/0000-0002-5993-1059
                Journal
                Journal ID (nlm-ta): Dis Markers
                Journal ID (iso-abbrev): Dis. Markers
                Journal ID (publisher-id): DM
                Title: Disease Markers
                Publisher: Hindawi
                ISSN (Print): 0278-0240
                ISSN (Electronic): 1875-8630
                Publication date Collection: 2019
                Publication date (Electronic): 3 March 2019
                Volume: 2019
                Electronic Location Identifier: 2673543
                Affiliations
                1Department of Medicine, University of Hong Kong, Queen Mary Hospital, 999077, Hong Kong
                2Asbestos Disease Research Institute, Sydney Medical School, University of Sydney, Rhodes, NSW 2139, Australia
                Author notes

                Guest Editor: Giuseppe Palmieri

                Author information
                http://orcid.org/0000-0001-6745-3483
                http://orcid.org/0000-0001-7060-0624
                http://orcid.org/0000-0002-5993-1059
                Article
                DOI: 10.1155/2019/2673543
                PMC ID: 6421784
                SO-VID: 95996855-1fe0-4f0a-b8f7-33451d5749d0
                Copyright © Copyright © 2019 Zhiyao Ma et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 24 September 2018
                Date accepted : 22 November 2018
                Categories
                Subject: Review Article

                Data availability:

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