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Phospholipase C Isozymes Are Deregulated in Colorectal Cancer – Insights Gained from Gene Set Enrichment Analysis of the Transcriptome

Colorectal cancer (CRC) is one of the most common cancer types in developed countries. To identify molecular networks and biological processes that are deregulated in CRC compared to normal colonic mucosa, we applied Gene Set Enrichment Analysis to two independent transcriptome datasets, including a...

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Autores principales: Danielsen, Stine A., Cekaite, Lina, Ågesen, Trude H., Sveen, Anita, Nesbakken, Arild, Thiis-Evensen, Espen, Skotheim, Rolf I., Lind, Guro E., Lothe, Ragnhild A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164721/
https://www.ncbi.nlm.nih.gov/pubmed/21909432
http://dx.doi.org/10.1371/journal.pone.0024419
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author Danielsen, Stine A.
Cekaite, Lina
Ågesen, Trude H.
Sveen, Anita
Nesbakken, Arild
Thiis-Evensen, Espen
Skotheim, Rolf I.
Lind, Guro E.
Lothe, Ragnhild A.
author_facet Danielsen, Stine A.
Cekaite, Lina
Ågesen, Trude H.
Sveen, Anita
Nesbakken, Arild
Thiis-Evensen, Espen
Skotheim, Rolf I.
Lind, Guro E.
Lothe, Ragnhild A.
author_sort Danielsen, Stine A.
collection PubMed
description Colorectal cancer (CRC) is one of the most common cancer types in developed countries. To identify molecular networks and biological processes that are deregulated in CRC compared to normal colonic mucosa, we applied Gene Set Enrichment Analysis to two independent transcriptome datasets, including a total of 137 CRC and ten normal colonic mucosa samples. Eighty-two gene sets as described by the Kyoto Encyclopedia of Genes and Genomes database had significantly altered gene expression in both datasets. These included networks associated with cell division, DNA maintenance, and metabolism. Among signaling pathways with known changes in key genes, the “Phosphatidylinositol signaling network”, comprising part of the PI3K pathway, was found deregulated. The downregulated genes in this pathway included several members of the Phospholipase C protein family, and the reduced expression of two of these, PLCD1 and PLCE1, were successfully validated in CRC biopsies (n = 70) and cell lines (n = 19) by quantitative analyses. The repression of both genes was found associated with KRAS mutations (P = 0.005 and 0.006, respectively), and we observed that microsatellite stable carcinomas with reduced PLCD1 expression more frequently had TP53 mutations (P = 0.002). Promoter methylation analyses of PLCD1 and PLCE1 performed in cell lines and tumor biopsies revealed that methylation of PLCD1 can contribute to reduced expression in 40% of the microsatellite instable carcinomas. In conclusion, we have identified significantly deregulated pathways in CRC, and validated repression of PLCD1 and PLCE1 expression. This illustrates that the GSEA approach may guide discovery of novel biomarkers in cancer.
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spelling pubmed-31647212011-09-09 Phospholipase C Isozymes Are Deregulated in Colorectal Cancer – Insights Gained from Gene Set Enrichment Analysis of the Transcriptome Danielsen, Stine A. Cekaite, Lina Ågesen, Trude H. Sveen, Anita Nesbakken, Arild Thiis-Evensen, Espen Skotheim, Rolf I. Lind, Guro E. Lothe, Ragnhild A. PLoS One Research Article Colorectal cancer (CRC) is one of the most common cancer types in developed countries. To identify molecular networks and biological processes that are deregulated in CRC compared to normal colonic mucosa, we applied Gene Set Enrichment Analysis to two independent transcriptome datasets, including a total of 137 CRC and ten normal colonic mucosa samples. Eighty-two gene sets as described by the Kyoto Encyclopedia of Genes and Genomes database had significantly altered gene expression in both datasets. These included networks associated with cell division, DNA maintenance, and metabolism. Among signaling pathways with known changes in key genes, the “Phosphatidylinositol signaling network”, comprising part of the PI3K pathway, was found deregulated. The downregulated genes in this pathway included several members of the Phospholipase C protein family, and the reduced expression of two of these, PLCD1 and PLCE1, were successfully validated in CRC biopsies (n = 70) and cell lines (n = 19) by quantitative analyses. The repression of both genes was found associated with KRAS mutations (P = 0.005 and 0.006, respectively), and we observed that microsatellite stable carcinomas with reduced PLCD1 expression more frequently had TP53 mutations (P = 0.002). Promoter methylation analyses of PLCD1 and PLCE1 performed in cell lines and tumor biopsies revealed that methylation of PLCD1 can contribute to reduced expression in 40% of the microsatellite instable carcinomas. In conclusion, we have identified significantly deregulated pathways in CRC, and validated repression of PLCD1 and PLCE1 expression. This illustrates that the GSEA approach may guide discovery of novel biomarkers in cancer. Public Library of Science 2011-09-01 /pmc/articles/PMC3164721/ /pubmed/21909432 http://dx.doi.org/10.1371/journal.pone.0024419 Text en Danielsen et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Danielsen, Stine A.
Cekaite, Lina
Ågesen, Trude H.
Sveen, Anita
Nesbakken, Arild
Thiis-Evensen, Espen
Skotheim, Rolf I.
Lind, Guro E.
Lothe, Ragnhild A.
Phospholipase C Isozymes Are Deregulated in Colorectal Cancer – Insights Gained from Gene Set Enrichment Analysis of the Transcriptome
title Phospholipase C Isozymes Are Deregulated in Colorectal Cancer – Insights Gained from Gene Set Enrichment Analysis of the Transcriptome
title_full Phospholipase C Isozymes Are Deregulated in Colorectal Cancer – Insights Gained from Gene Set Enrichment Analysis of the Transcriptome
title_fullStr Phospholipase C Isozymes Are Deregulated in Colorectal Cancer – Insights Gained from Gene Set Enrichment Analysis of the Transcriptome
title_full_unstemmed Phospholipase C Isozymes Are Deregulated in Colorectal Cancer – Insights Gained from Gene Set Enrichment Analysis of the Transcriptome
title_short Phospholipase C Isozymes Are Deregulated in Colorectal Cancer – Insights Gained from Gene Set Enrichment Analysis of the Transcriptome
title_sort phospholipase c isozymes are deregulated in colorectal cancer – insights gained from gene set enrichment analysis of the transcriptome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164721/
https://www.ncbi.nlm.nih.gov/pubmed/21909432
http://dx.doi.org/10.1371/journal.pone.0024419
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