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Conserved Molecular Underpinnings and Characterization of a Role for Caveolin-1 in the Tumor Microenvironment of Mature T-Cell Lymphomas.

Herek TA, Shew TD, Spurgin HN, Cutucache CE - PLoS ONE (2015)

Bottom Line: Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics.From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors.Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Nebraska at Omaha, Omaha, Nebraska, United States of America.

ABSTRACT
Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics. Much work has been done to gain greater insights into distinguishing features among malignant subtypes, but there also exists a need to identify unifying characteristics to assist in rapid diagnosis and subsequent potential treatment. Herein, we investigated gene expression data of five different mature T-cell lymphoma subtypes (n = 187) and found 21 genes to be up- and down-regulated across all malignancies in comparison to healthy CD4(+) and CD8(+) T-cell controls (n = 52). From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors. Caveolin-1 was upregulated, albeit with a heterogeneous nature, across all mature T-cell lymphoma subtypes, a finding confirmed using immunohistochemical staining on an independent sampling of mature T-cell lymphoma biopsies (n = 65 cases). Further, stratifying malignant samples in accordance with high and low CAV1 expression revealed that higher expression of CAV1 in mature T-cell lymphomas is analogous with an enhanced inflammatory and invasive gene expression profile. Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications.

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Related in: MedlinePlus

Construction of a shared T-cell compartment gene signature across mature T-cell lymphomas.(A) Heatmap of genes (n = 6) significantly (p < 0.001, FDR < 0.001) upregulated across all T-cell lymphoma subtypes as compared with healthy controls. Genes are mean-centered, standard-deviation scaled, and clustered according to average linkage. Samples are aligned according to healthy (purple bar) or malignant (orange bar) designations. (B) Heatmap of genes (n = 15) significantly (p < 0.001, FDR < 0.001) downregulated across all T-cell lymphoma subtypes as compared to healthy controls. Genes are mean-centered, standard-deviation scaled, and clustered according to average linkage. Samples are aligned according to healthy (purple bar) or malignant (orange bar) designations. (C) Boxplot of normalized 212097_at (CAV1) probe signal across sample types. Continuous line represents median value of sample, discontinuous line represents mean value. (D) Boxplot of normalized 1557257_at (BCL10) probe signal for representation. Continuous line represents median value of sample, discontinuous line represents mean value.
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pone.0142682.g001: Construction of a shared T-cell compartment gene signature across mature T-cell lymphomas.(A) Heatmap of genes (n = 6) significantly (p < 0.001, FDR < 0.001) upregulated across all T-cell lymphoma subtypes as compared with healthy controls. Genes are mean-centered, standard-deviation scaled, and clustered according to average linkage. Samples are aligned according to healthy (purple bar) or malignant (orange bar) designations. (B) Heatmap of genes (n = 15) significantly (p < 0.001, FDR < 0.001) downregulated across all T-cell lymphoma subtypes as compared to healthy controls. Genes are mean-centered, standard-deviation scaled, and clustered according to average linkage. Samples are aligned according to healthy (purple bar) or malignant (orange bar) designations. (C) Boxplot of normalized 212097_at (CAV1) probe signal across sample types. Continuous line represents median value of sample, discontinuous line represents mean value. (D) Boxplot of normalized 1557257_at (BCL10) probe signal for representation. Continuous line represents median value of sample, discontinuous line represents mean value.

Mentions: In order to delineate a shared T-cell compartment signature among a diverse grouping of mature T-cell lymphomas, we conducted differential expression analyses of the five different mature T-cell lymphoma subtypes collected, focusing on GO annotations specific to T-cell biology. We analyzed each T-cell lymphoma subtype separately, with a final manual compilation of genes found to be differentially expressed across all subtypes. This analysis revealed an up-regulation of 6 genes (namely CAV1, CCNB2, ENAH, PSEN2, THY1, TNFRSF21) (Fig 1A) and a down-regulation of 15 genes (namely BCL10, CD3G, CD5, FOXP1, IL23A, ITK, LAT, PAG1, PDE4B, PRKCQ, RICTOR, STAT5A, TNFRSF14, TSC22D3, UBASH3A) (Fig 1B) that were observed to be differentially expressed (p < 0.001, FDR < 0.001) in all T-cell lymphoma subtypes (Table 2). Further, 52 genes were found to either be up- or down-regulated in at least 3 out of 5 of the analyzed subtypes (S1 Table).


Conserved Molecular Underpinnings and Characterization of a Role for Caveolin-1 in the Tumor Microenvironment of Mature T-Cell Lymphomas.

Herek TA, Shew TD, Spurgin HN, Cutucache CE - PLoS ONE (2015)

Construction of a shared T-cell compartment gene signature across mature T-cell lymphomas.(A) Heatmap of genes (n = 6) significantly (p < 0.001, FDR < 0.001) upregulated across all T-cell lymphoma subtypes as compared with healthy controls. Genes are mean-centered, standard-deviation scaled, and clustered according to average linkage. Samples are aligned according to healthy (purple bar) or malignant (orange bar) designations. (B) Heatmap of genes (n = 15) significantly (p < 0.001, FDR < 0.001) downregulated across all T-cell lymphoma subtypes as compared to healthy controls. Genes are mean-centered, standard-deviation scaled, and clustered according to average linkage. Samples are aligned according to healthy (purple bar) or malignant (orange bar) designations. (C) Boxplot of normalized 212097_at (CAV1) probe signal across sample types. Continuous line represents median value of sample, discontinuous line represents mean value. (D) Boxplot of normalized 1557257_at (BCL10) probe signal for representation. Continuous line represents median value of sample, discontinuous line represents mean value.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643970&req=5

pone.0142682.g001: Construction of a shared T-cell compartment gene signature across mature T-cell lymphomas.(A) Heatmap of genes (n = 6) significantly (p < 0.001, FDR < 0.001) upregulated across all T-cell lymphoma subtypes as compared with healthy controls. Genes are mean-centered, standard-deviation scaled, and clustered according to average linkage. Samples are aligned according to healthy (purple bar) or malignant (orange bar) designations. (B) Heatmap of genes (n = 15) significantly (p < 0.001, FDR < 0.001) downregulated across all T-cell lymphoma subtypes as compared to healthy controls. Genes are mean-centered, standard-deviation scaled, and clustered according to average linkage. Samples are aligned according to healthy (purple bar) or malignant (orange bar) designations. (C) Boxplot of normalized 212097_at (CAV1) probe signal across sample types. Continuous line represents median value of sample, discontinuous line represents mean value. (D) Boxplot of normalized 1557257_at (BCL10) probe signal for representation. Continuous line represents median value of sample, discontinuous line represents mean value.
Mentions: In order to delineate a shared T-cell compartment signature among a diverse grouping of mature T-cell lymphomas, we conducted differential expression analyses of the five different mature T-cell lymphoma subtypes collected, focusing on GO annotations specific to T-cell biology. We analyzed each T-cell lymphoma subtype separately, with a final manual compilation of genes found to be differentially expressed across all subtypes. This analysis revealed an up-regulation of 6 genes (namely CAV1, CCNB2, ENAH, PSEN2, THY1, TNFRSF21) (Fig 1A) and a down-regulation of 15 genes (namely BCL10, CD3G, CD5, FOXP1, IL23A, ITK, LAT, PAG1, PDE4B, PRKCQ, RICTOR, STAT5A, TNFRSF14, TSC22D3, UBASH3A) (Fig 1B) that were observed to be differentially expressed (p < 0.001, FDR < 0.001) in all T-cell lymphoma subtypes (Table 2). Further, 52 genes were found to either be up- or down-regulated in at least 3 out of 5 of the analyzed subtypes (S1 Table).

Bottom Line: Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics.From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors.Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Nebraska at Omaha, Omaha, Nebraska, United States of America.

ABSTRACT
Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics. Much work has been done to gain greater insights into distinguishing features among malignant subtypes, but there also exists a need to identify unifying characteristics to assist in rapid diagnosis and subsequent potential treatment. Herein, we investigated gene expression data of five different mature T-cell lymphoma subtypes (n = 187) and found 21 genes to be up- and down-regulated across all malignancies in comparison to healthy CD4(+) and CD8(+) T-cell controls (n = 52). From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors. Caveolin-1 was upregulated, albeit with a heterogeneous nature, across all mature T-cell lymphoma subtypes, a finding confirmed using immunohistochemical staining on an independent sampling of mature T-cell lymphoma biopsies (n = 65 cases). Further, stratifying malignant samples in accordance with high and low CAV1 expression revealed that higher expression of CAV1 in mature T-cell lymphomas is analogous with an enhanced inflammatory and invasive gene expression profile. Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications.

Show MeSH
Related in: MedlinePlus