Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients

Abstract Background Patients with early colorectal cancer (stages I–II) generally have a good prognosis, but a subgroup of 15–20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disea...

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Main Authors: Guro E. Lind, Marianne Guriby, Terje Ahlquist, Israr Hussain, Marine Jeanmougin, Kjetil Søreide, Hartwig Kørner, Ragnhild A. Lothe, Oddmund Nordgård
Format: Article
Language:English
Published: BMC 2017-09-01
Series:Clinical Epigenetics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13148-017-0397-4
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author Guro E. Lind
Marianne Guriby
Terje Ahlquist
Israr Hussain
Marine Jeanmougin
Kjetil Søreide
Hartwig Kørner
Ragnhild A. Lothe
Oddmund Nordgård
author_facet Guro E. Lind
Marianne Guriby
Terje Ahlquist
Israr Hussain
Marine Jeanmougin
Kjetil Søreide
Hartwig Kørner
Ragnhild A. Lothe
Oddmund Nordgård
author_sort Guro E. Lind
collection DOAJ
description Abstract Background Patients with early colorectal cancer (stages I–II) generally have a good prognosis, but a subgroup of 15–20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients. Results The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage (P = 8.2E−17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P = 3.0E−4; time to recurrence P = 3.1E−4), although not significant. The same trend was observed in multivariate analyses (P = 1.4E−1 and P = 6.7E−2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I–II) colon cancer patients who experienced relapse. Conclusions Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.
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spelling doaj.art-08a534a705a04ef3ae86ef57bfc08c4e2022-12-21T18:53:19ZengBMCClinical Epigenetics1868-70751868-70832017-09-01911810.1186/s13148-017-0397-4Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patientsGuro E. Lind0Marianne Guriby1Terje Ahlquist2Israr Hussain3Marine Jeanmougin4Kjetil Søreide5Hartwig Kørner6Ragnhild A. Lothe7Oddmund Nordgård8Department of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University HospitalDepartment of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University HospitalDepartment of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University HospitalDepartment of Hematology and Oncology, Stavanger University HospitalDepartment of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University HospitalDepartment of Gastrointestinal Surgery, Stavanger University HospitalDepartment of Gastrointestinal Surgery, Stavanger University HospitalDepartment of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University HospitalDepartment of Hematology and Oncology, Stavanger University HospitalAbstract Background Patients with early colorectal cancer (stages I–II) generally have a good prognosis, but a subgroup of 15–20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients. Results The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage (P = 8.2E−17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P = 3.0E−4; time to recurrence P = 3.1E−4), although not significant. The same trend was observed in multivariate analyses (P = 1.4E−1 and P = 6.7E−2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I–II) colon cancer patients who experienced relapse. Conclusions Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.http://link.springer.com/article/10.1186/s13148-017-0397-4BiomarkersDNA methylationOccult metastasesPrognosisRelapseSentinel lymph nodes
spellingShingle Guro E. Lind
Marianne Guriby
Terje Ahlquist
Israr Hussain
Marine Jeanmougin
Kjetil Søreide
Hartwig Kørner
Ragnhild A. Lothe
Oddmund Nordgård
Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients
Clinical Epigenetics
Biomarkers
DNA methylation
Occult metastases
Prognosis
Relapse
Sentinel lymph nodes
title Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients
title_full Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients
title_fullStr Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients
title_full_unstemmed Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients
title_short Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients
title_sort prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients
topic Biomarkers
DNA methylation
Occult metastases
Prognosis
Relapse
Sentinel lymph nodes
url http://link.springer.com/article/10.1186/s13148-017-0397-4
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