Dataset Information

Cellular heterogeneity contributes to subtype-specific expression of ZEB1 in human glioblastoma.

ABSTRACT: The transcription factor ZEB1 has gained attention in tumor biology of epithelial cancers because of its function in epithelial-mesenchymal transition, DNA repair, stem cell biology and tumor-induced immunosuppression, but its role in gliomas with respect to invasion and prognostic value is controversial. We characterized ZEB1 expression at single cell level in 266 primary brain tumors and present a comprehensive dataset of high grade gliomas with Ki67, p53, IDH1, and EGFR immunohistochemistry, as well as EGFR FISH. ZEB1 protein expression in glioma stem cell lines was compared to their parental tumors with respect to gene expression subtypes based on RNA-seq transcriptomic profiles. ZEB1 is widely expressed in glial tumors, but in a highly variable fraction of cells. In glioblastoma, ZEB1 labeling index is higher in tumors with EGFR amplification or IDH1 mutation. Co-labeling studies showed that tumor cells and reactive astroglia, but not immune cells contribute to the ZEB1 positive population. In contrast, glioma cell lines constitutively express ZEB1 irrespective of gene expression subtype. In conclusion, our data indicate that immune infiltration likely contributes to differential labelling of ZEB1 and confounds interpretation of bulk ZEB1 expression data.

SUBMITTER: Euskirchen P

PROVIDER: S-EPMC5612763 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Cellular heterogeneity contributes to subtype-specific expression of ZEB1 in human glioblastoma.

Euskirchen Philipp P Radke Josefine J Schmidt Marc Sören MS Schulze Heuling Eva E Kadikowski Eric E Maricos Meron M Knab Felix F Grittner Ulrike U Zerbe Norman N Czabanka Marcus M Dieterich Christoph C Miletic Hrvoje H Mørk Sverre S Koch Arend A Endres Matthias M Harms Christoph C

PloS one 20170925 9

The transcription factor ZEB1 has gained attention in tumor biology of epithelial cancers because of its function in epithelial-mesenchymal transition, DNA repair, stem cell biology and tumor-induced immunosuppression, but its role in gliomas with respect to invasion and prognostic value is controversial. We characterized ZEB1 expression at single cell level in 266 primary brain tumors and present a comprehensive dataset of high grade gliomas with Ki67, p53, IDH1, and EGFR immunohistochemistry, ...[more]

PMID: 28945795

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Project description:Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2-neu) of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs) within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC) and six Her2+. We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER+ cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs may contribute to the more invasive properties and unfavorable prognosis of Her2+ breast cancer. These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer. We isolated CAFs from twenty primary breast cancer samples representing three main subtypes (ER+ (n=7), TNBC (n=7), Her2+ (n=6)) and performed gene expression profile analyses on RNA isolated from these early passage CAFs. Those samples were done in two batches with 4 samples repeated in both batches. One TNBC sample was found to be an outlier and not used in the analysis.

Dataset Information

Cellular heterogeneity contributes to subtype-specific expression of ZEB1 in human glioblastoma.

Publications

Cellular heterogeneity contributes to subtype-specific expression of ZEB1 in human glioblastoma.

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