Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype
Sara Cherradi, Pierre Martineau, Céline Gongora, Maguy Del Rio Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France Purpose: Colorectal...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-02-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/claudin-gene-expression-profiles-and-clinical-value-in-colorectal-tumo-peer-reviewed-article-CMAR |
| _version_ | 1818908254685626368 |
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| author | Cherradi S Martineau P Gongora C Del Rio M |
| author_facet | Cherradi S Martineau P Gongora C Del Rio M |
| author_sort | Cherradi S |
| collection | DOAJ |
| description | Sara Cherradi, Pierre Martineau, Céline Gongora, Maguy Del Rio Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France Purpose: Colorectal cancer (CRC) is a heterogeneous disease that can be classified into distinct molecular subtypes. The aims of this study were 1) to compare claudin (CLDN) gene expression in CRC samples and normal colon mucosa, and then in the different CRC molecular subtypes, and 2) to assess their prognostic value.Patients and methods: CLDN expression in CRC samples was analyzed using gene expression data for a cohort of 143 primary CRC samples, and compared in the same CRC samples classified into different molecular subtypes (C1 to C6 according to the Marisa’s classification, and CMS1 to CMS4 of the consensus classification). Comparison of CLDN expression in normal and tumor colon samples was also made on a smaller number of samples. Then, the relationship between CLDN expression profiles and overall survival (OS) and progression-free survival was examined.Results: Compared with normal mucosa, CLDN1 and CLDN2 were upregulated, whereas CLDN5, 7, 8, and 23 were downregulated in CRC samples. Variations in CLDN expression profiles were observed mainly in the CMS2/C1 and CMS4/C4 subtypes. Overall, expression of CLDN2 or CLDN4 alone had a strong prognostic value that increased when they were associated. In the CMS4/C4 subtypes, lower expressions of CLDN11, CLDN12, and CLDN23 were associated with longer OS. Conversely, in the CMS2 and C1 subtypes, low CLDN23 expression was associated with shorter OS and progression-free survival, suggesting a dual role for CLDN23 as a tumor suppressor/promoter in CRC. CLDN6 and CLDN11 had a prognostic value in the CMS2 and C4 subtypes, respectively.Conclusion: This analysis of CLDN gene expression profiles and prognostic value in CRC samples classified according to their molecular subtype shows that CRC heterogeneity must be taken into account when assessing CLDN potential value as prognostic markers or therapeutic targets. Keywords: colon, cancer, classification, prognosis, claudin, target, tight junction, heterogeneity |
| first_indexed | 2024-12-19T22:08:06Z |
| format | Article |
| id | doaj.art-4176946cbdb84299b9986f7f4a580778 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-19T22:08:06Z |
| publishDate | 2019-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-4176946cbdb84299b9986f7f4a5807782022-12-21T20:03:58ZengDove Medical PressCancer Management and Research1179-13222019-02-01Volume 111337134844062Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtypeCherradi SMartineau PGongora CDel Rio MSara Cherradi, Pierre Martineau, Céline Gongora, Maguy Del Rio Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France Purpose: Colorectal cancer (CRC) is a heterogeneous disease that can be classified into distinct molecular subtypes. The aims of this study were 1) to compare claudin (CLDN) gene expression in CRC samples and normal colon mucosa, and then in the different CRC molecular subtypes, and 2) to assess their prognostic value.Patients and methods: CLDN expression in CRC samples was analyzed using gene expression data for a cohort of 143 primary CRC samples, and compared in the same CRC samples classified into different molecular subtypes (C1 to C6 according to the Marisa’s classification, and CMS1 to CMS4 of the consensus classification). Comparison of CLDN expression in normal and tumor colon samples was also made on a smaller number of samples. Then, the relationship between CLDN expression profiles and overall survival (OS) and progression-free survival was examined.Results: Compared with normal mucosa, CLDN1 and CLDN2 were upregulated, whereas CLDN5, 7, 8, and 23 were downregulated in CRC samples. Variations in CLDN expression profiles were observed mainly in the CMS2/C1 and CMS4/C4 subtypes. Overall, expression of CLDN2 or CLDN4 alone had a strong prognostic value that increased when they were associated. In the CMS4/C4 subtypes, lower expressions of CLDN11, CLDN12, and CLDN23 were associated with longer OS. Conversely, in the CMS2 and C1 subtypes, low CLDN23 expression was associated with shorter OS and progression-free survival, suggesting a dual role for CLDN23 as a tumor suppressor/promoter in CRC. CLDN6 and CLDN11 had a prognostic value in the CMS2 and C4 subtypes, respectively.Conclusion: This analysis of CLDN gene expression profiles and prognostic value in CRC samples classified according to their molecular subtype shows that CRC heterogeneity must be taken into account when assessing CLDN potential value as prognostic markers or therapeutic targets. Keywords: colon, cancer, classification, prognosis, claudin, target, tight junction, heterogeneityhttps://www.dovepress.com/claudin-gene-expression-profiles-and-clinical-value-in-colorectal-tumo-peer-reviewed-article-CMARColoncancerclassificationprognosisclaudintarget. |
| spellingShingle | Cherradi S Martineau P Gongora C Del Rio M Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype Cancer Management and Research Colon cancer classification prognosis claudin target. |
| title | Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype |
| title_full | Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype |
| title_fullStr | Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype |
| title_full_unstemmed | Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype |
| title_short | Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype |
| title_sort | claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype |
| topic | Colon cancer classification prognosis claudin target. |
| url | https://www.dovepress.com/claudin-gene-expression-profiles-and-clinical-value-in-colorectal-tumo-peer-reviewed-article-CMAR |
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