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      Detection of Methylated SEPT9 in Plasma Is a Reliable Screening Method for Both Left- and Right-Sided Colon Cancers

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          Abstract

          Background

          Methylated Septin 9 (SEPT9) is a sensitive biomarker for colorectal cancer (CRC) from peripheral blood. However, its relationship to cancer localization, guaiac-based fecal occult blood test (gFOBT) and carcinoembryonic antigen (CEA) have not been described.

          Methodology/Principal Findings

          Plasma samples were collected for SEPT9 analysis from patients with no evidence of disease (NED) (n = 92) before colonoscopy and CRC (n = 92) before surgical treatment. DNA was isolated and bisulfite-converted using Epi proColon kit 2.0. Qualitative determination was performed using Epi proColon 2.0 RT-PCR assay. Samples for gFOBT and CEA analysis were collected from NED (n = 17 and 27, respectively) and CRC (n = 22 and 27, respectively). SEPT9 test was positive in 15.2% (14/92) of NED and 95.6% (88/92) of CRC, including 100% (67/67) from stage II to stage IV CRC and 84% (21/25) of stage I CRC when a sample was called positive if 1 out of 3 PCR replicates was positive. In a second analysis (2 out of 3 PCR replicates) specificity improved to 99% (91/92) of NEDs, at a sensitivity of 79.3% (73/92) of SEPT9 positives in CRC. gFOBT was positive in 29.4% (5/17) of NED and 68.2% (15/22) of CRC and elevated CEA levels were detected in 14.8% (4/27) of NED and 51.8% (14/27) of CRC. Both SEPT9 (84.8%) and CEA (85.2%) showed higher specificity than gFOBT (70.6%). SEPT9 was positive in 96.4% (54/56) of left-sided colon cancer (LSCC) cases and 94.4% (34/36) of right-sided colon cancer (RSCC) cases. gFOBT was positive in 83.3% (10/12) of cases with LSCC and 50% (5/10) of cases with RSCC, elevated CEA was detected 60% (9/15) of LSCC and 41.7% (5/12) of RSCC.

          Conclusions/Significance

          The high degree of sensitivity and specificity of SEPT9 in plasma makes it a better method to detect CRC than gFOBT and CEA, even for the more difficult to detect RSCC.

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          Most cited references 25

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          Global cancer statistics

           A. JEMAL,  F BRAY,  MM Center (2011)
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              Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.

              In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average-risk adults. In this update of each organization's guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that primarily is effective at early cancer detection and a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                25 September 2012
                : 7
                : 9
                Affiliations
                [1 ]2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
                [2 ]Molecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest, Hungary
                [3 ]Institute for Pathology, Universitätsklinikum Erlangen, Erlagen, Germany
                [4 ]Department of Surgery, Universitätsklinikum Erlangen, Erlagen, Germany
                Sun Yat-sen University Cancer Center, China
                Author notes

                Competing Interests: This study was supported by Epigenomics AG (Berlin, Germany). The sponsor has partially supplied the reagents for the study, performed technical training and support. The authors declare that they are not employed and not consultants at the funder. The authors have no share in patents, products in development or marketed products. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: BM ZST. Performed the experiments: KT FS AK ÁVP. Analyzed the data: KT BW. Contributed reagents/materials/analysis tools: FS BM ZST RS HG VS. Wrote the paper: KT FS HG BM.

                Article
                PONE-D-12-09691
                10.1371/journal.pone.0046000
                3457959
                23049919

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 7
                Funding
                This study was supported by Epigenomics AG (Berlin, Germany). The sponsor has partially supplied the reagents for the study, performed technical training and support. Data collection, decision to publish and preparation of the manuscript were performed by the authors.
                Categories
                Research Article
                Medicine
                Diagnostic Medicine
                Pathology
                General Pathology
                Biomarkers
                Epidemiology
                Biomarker Epidemiology
                Cancer Epidemiology
                Gastroenterology and Hepatology
                Gastrointestinal Cancers
                Oncology
                Cancer Detection and Diagnosis
                Cancer Screening
                Early Detection
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Colon Adenocarcinoma
                Rectal Cancer
                Basic Cancer Research

                Uncategorized

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