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A Tissue-Based Comparative Effectiveness Analysis of Biomarkers for Early Detection of Colorectal Tumors

OBJECTIVES: We recently identified a six-gene methylation-based biomarker panel suitable for early detection of colorectal cancer (CRC). In this study, we compared the performance of this novel epi-panel with that of previously identified DNA methylation markers in the same clinical tissue sample se...

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Autores principales: Ahmed, Deeqa, Danielsen, Stine A, Aagesen, Trude H, Bretthauer, Michael, Thiis-Evensen, Espen, Hoff, Geir, Rognum, Torleiv O, Nesbakken, Arild, Lothe, Ragnhild A, Lind, Guro E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535074/
https://www.ncbi.nlm.nih.gov/pubmed/23324654
http://dx.doi.org/10.1038/ctg.2012.21
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author Ahmed, Deeqa
Danielsen, Stine A
Aagesen, Trude H
Bretthauer, Michael
Thiis-Evensen, Espen
Hoff, Geir
Rognum, Torleiv O
Nesbakken, Arild
Lothe, Ragnhild A
Lind, Guro E
author_facet Ahmed, Deeqa
Danielsen, Stine A
Aagesen, Trude H
Bretthauer, Michael
Thiis-Evensen, Espen
Hoff, Geir
Rognum, Torleiv O
Nesbakken, Arild
Lothe, Ragnhild A
Lind, Guro E
author_sort Ahmed, Deeqa
collection PubMed
description OBJECTIVES: We recently identified a six-gene methylation-based biomarker panel suitable for early detection of colorectal cancer (CRC). In this study, we compared the performance of this novel epi-panel with that of previously identified DNA methylation markers in the same clinical tissue sample sets. METHODS: Quantitative methylation-specific PCR was used to analyze the promoter region of SEPT9 and VIM in a total of 485 tissue samples, divided into test and validation sets. ITGA4, NTRK2, OSMR, and TUBG2 were also included in the analyses. Receiver operating characteristic (ROC) curves were used to compare the performances of the individual biomarkers with that of the novel epi-panel. RESULTS: SEPT9 and VIM were methylated in 82 and 67% of CRCs (n=169) and in 88 and 54% of the adenomas (n=104). Only 3% of the normal mucosa samples (n=107) were methylated for these genes, confirming that the methylation was highly cancer-specific. Areas under the ROC curve (AUC), distinguishing CRCs from normal mucosa, were 0.94 for SEPT9 and 0.81 for VIM. AUC values for separating adenomas from normal mucosa samples were 0.96 and 0.81 for the same genes. In comparison, the novel epi-panel achieved an AUC of 0.98 (CRC) and 0.97 (adenomas). ITGA4, OSMR, NTRK2, and TUBG2 were methylated in 90, 78, 7, and 1% of the CRCs, and in 76, 77, 3, and 0% of the adenomas. Between 0 and 2% of the normal mucosa samples were methylated for the same genes. ITGA4 and OSMR achieved an AUC of 0.96 and 0.92 (CRC vs. normal mucosa), and 0.93 and 0.92 (adenomas vs. normal mucosa). CONCLUSIONS: We have confirmed the high performance of some of the previously identified DNA methylation markers. Furthermore, we showed that a recently reported epi-panel performed better than the individual DNA methylation biomarkers when analyzed in the same tissue samples. This observation was also true for VIM and SEPT9, which are included in commercially available noninvasive tests for CRC. These results further underscore the value of combining a manageable number of individual markers into a panel, which in addition to having a higher sensitivity and specificity might provide a more profound robustness to a noninvasive test compared with single markers.
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spelling pubmed-35350742013-01-03 A Tissue-Based Comparative Effectiveness Analysis of Biomarkers for Early Detection of Colorectal Tumors Ahmed, Deeqa Danielsen, Stine A Aagesen, Trude H Bretthauer, Michael Thiis-Evensen, Espen Hoff, Geir Rognum, Torleiv O Nesbakken, Arild Lothe, Ragnhild A Lind, Guro E Clin Transl Gastroenterol Liver OBJECTIVES: We recently identified a six-gene methylation-based biomarker panel suitable for early detection of colorectal cancer (CRC). In this study, we compared the performance of this novel epi-panel with that of previously identified DNA methylation markers in the same clinical tissue sample sets. METHODS: Quantitative methylation-specific PCR was used to analyze the promoter region of SEPT9 and VIM in a total of 485 tissue samples, divided into test and validation sets. ITGA4, NTRK2, OSMR, and TUBG2 were also included in the analyses. Receiver operating characteristic (ROC) curves were used to compare the performances of the individual biomarkers with that of the novel epi-panel. RESULTS: SEPT9 and VIM were methylated in 82 and 67% of CRCs (n=169) and in 88 and 54% of the adenomas (n=104). Only 3% of the normal mucosa samples (n=107) were methylated for these genes, confirming that the methylation was highly cancer-specific. Areas under the ROC curve (AUC), distinguishing CRCs from normal mucosa, were 0.94 for SEPT9 and 0.81 for VIM. AUC values for separating adenomas from normal mucosa samples were 0.96 and 0.81 for the same genes. In comparison, the novel epi-panel achieved an AUC of 0.98 (CRC) and 0.97 (adenomas). ITGA4, OSMR, NTRK2, and TUBG2 were methylated in 90, 78, 7, and 1% of the CRCs, and in 76, 77, 3, and 0% of the adenomas. Between 0 and 2% of the normal mucosa samples were methylated for the same genes. ITGA4 and OSMR achieved an AUC of 0.96 and 0.92 (CRC vs. normal mucosa), and 0.93 and 0.92 (adenomas vs. normal mucosa). CONCLUSIONS: We have confirmed the high performance of some of the previously identified DNA methylation markers. Furthermore, we showed that a recently reported epi-panel performed better than the individual DNA methylation biomarkers when analyzed in the same tissue samples. This observation was also true for VIM and SEPT9, which are included in commercially available noninvasive tests for CRC. These results further underscore the value of combining a manageable number of individual markers into a panel, which in addition to having a higher sensitivity and specificity might provide a more profound robustness to a noninvasive test compared with single markers. Nature Publishing Group 2012-12 2012-12-06 /pmc/articles/PMC3535074/ /pubmed/23324654 http://dx.doi.org/10.1038/ctg.2012.21 Text en Copyright © 2012 American College of Gastroenterology http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Liver
Ahmed, Deeqa
Danielsen, Stine A
Aagesen, Trude H
Bretthauer, Michael
Thiis-Evensen, Espen
Hoff, Geir
Rognum, Torleiv O
Nesbakken, Arild
Lothe, Ragnhild A
Lind, Guro E
A Tissue-Based Comparative Effectiveness Analysis of Biomarkers for Early Detection of Colorectal Tumors
title A Tissue-Based Comparative Effectiveness Analysis of Biomarkers for Early Detection of Colorectal Tumors
title_full A Tissue-Based Comparative Effectiveness Analysis of Biomarkers for Early Detection of Colorectal Tumors
title_fullStr A Tissue-Based Comparative Effectiveness Analysis of Biomarkers for Early Detection of Colorectal Tumors
title_full_unstemmed A Tissue-Based Comparative Effectiveness Analysis of Biomarkers for Early Detection of Colorectal Tumors
title_short A Tissue-Based Comparative Effectiveness Analysis of Biomarkers for Early Detection of Colorectal Tumors
title_sort tissue-based comparative effectiveness analysis of biomarkers for early detection of colorectal tumors
topic Liver
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535074/
https://www.ncbi.nlm.nih.gov/pubmed/23324654
http://dx.doi.org/10.1038/ctg.2012.21
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