Dataset Information

Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas.

ABSTRACT: BACKGROUND:Meningiomas are the most common intracranial tumors, with a subset of cases bearing a progressive phenotype. The DCC netrin 1 receptor (DCC) is a candidate gene for early meningioma progression. Cancer stem cell (CSC) genes are emerging as cancer therapeutic targets, as their expression is frequently associated with aggressive tumor phenotypes. The main objective of the study was to identify deregulated CSC genes in meningiomas. MATERIALS AND METHODS:Interrogating two expression data repositories, significantly differentially expressed genes (DEGs) were determined using DCC low vs. DCC high expression groups and WHO grade I (GI) vs. grade II + grade III (GII + GIII) comparison groups. Human stem cell (SC) genes were compiled from two published data sets and were extracted from the DEG lists. Biofunctional analysis was performed to assess associations between genes or molecules. RESULTS:In the DCC low vs. DCC high expression groups, we assessed seven studies representing each between seven and 58 samples. The type I transmembrane protein podocalyxin like (PODXL) was markedly upregulated in DCC low expression meningiomas in six studies. Other CSC genes repeatedly deregulated included, e.g., BMP/retinoic acid inducible neural specific 1 (BRINP1), prominin 1 (PROM1), solute carrier family 24 member 3 (SLC24A3), rRho GTPase activating protein 28 (ARHGAP28), Kruppel like factor 5 (KLF5), and leucine rich repeat containing G protein-coupled receptor 4 (LGR4). In the GI vs. GII + GIII comparison groups, we assessed six studies representing each between nine and 68 samples. DNA topoisomerase 2-alpha (TOP2A) was markedly upregulated in GII + GIII meningiomas in four studies. Other CSC genes repeatedly deregulated included, e.g., ARHGAP28 and PODXL. Network analysis revealed associations of molecules with, e.g., cellular development and movement; nervous system development and function; and cancer. CONCLUSIONS:This meta-analysis on meningiomas identified a comprehensive list of deregulated CSC genes across different array expression studies. Especially, PODXL is of interest for functional assessment in progressive meningiomas.

SUBMITTER: Schulten HJ

PROVIDER: S-EPMC6513070 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas.

Schulten Hans-Juergen HJ Hussein Deema D

PloS one 20190513 5

<h4>Background</h4>Meningiomas are the most common intracranial tumors, with a subset of cases bearing a progressive phenotype. The DCC netrin 1 receptor (DCC) is a candidate gene for early meningioma progression. Cancer stem cell (CSC) genes are emerging as cancer therapeutic targets, as their expression is frequently associated with aggressive tumor phenotypes. The main objective of the study was to identify deregulated CSC genes in meningiomas.<h4>Materials and methods</h4>Interrogating two e ...[more]

PMID: 31083655

Similar Datasets

Project description:IntroductionMeningiomas are the most common primary central nervous system (CNS) tumors in adults, representing approximately one-third of all primary adult CNS tumors. Although several recent publications have proposed alternative grading systems of meningiomas that incorporate genomic and/or epigenomic data to better predict meningioma recurrence and progression-free survival, our understanding of driving forces of meningioma development is still limited.ObjectiveTo define gene expression signatures of the most common subtypes of meningiomas to better understand cellular processes and signaling pathways specific for each tumor genotype.MethodsWe used RNA sequencing (RNA-seq) to determine whole transcriptome profiles of twenty meningiomas with genomic alterations including NF2 inactivation, loss of chr1p, and missense mutations in TRAF7, AKT1 and KLF4.ResultsThe analysis revealed that meningiomas with NF2 gene inactivation expressed higher levels of BCL2 and GLI1 compared with tumors harboring TRAF7 missense mutations. Moreover, NF2 meningiomas were subdivided into two distinct groups based on additional loss of chr1p. NF2 tumors with intact chr1p were characterized by the high expression of tumor suppressor PTCH2 compared to NF2 tumors with chr1p loss. Taken together with the high expression of BCL2 and GLI1, these results suggest that activation of Sonic Hedgehog pathway may contribute to NF2 meningioma development. In contrast, NF2 tumors with chr1p loss expressed high levels of transcription factor FOXD3 and its antisense RNA FOXD3-AS1. Examination of TRAF7 tumors demonstrated that TRAF7 regulates a number of biomechanically responsive genes (KRT6a, KRT16, IL1RL1, and AQP3 among others). Interestingly, AKT1 and KLF4 meningiomas expressed genes specific for PI3K/AKT signaling pathway, suggesting overlapping gene signatures between the two subtypes. In addition, KLF4 meningiomas had high expression of carcinoembryonic antigen family members CEACAM6 and CEACAM5.ConclusionsEach group of meningiomas displayed a unique gene expression signature suggesting signaling pathways potentially implicated in tumorigenesis. These findings will improve our understanding of meningioma tumorigenesis and prognosis.

Dataset Information

Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas.

Publications

Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets