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.

Characterization of SALL2 Gene Isoforms and Targets Across Cell Types Reveals Highly Conserved Networks

“…It is overexpressed in various tumor cell types and is associated with their aggressiveness and poor prognosis ( Xu et al, 2018 ). PODXL upregulation is a cancer stem cell marker in meningiomas ( Schulten and Hussein, 2019 ) and a marker of poor outcome in patients with GBM ( Binder et al, 2013 ). It is proposed as a biomarker of poor prognosis in colorectal cancers also ( Larsson et al, 2012 , 2013 , 2016 ; Lee et al, 2017 ).…”

Landscape of Genome-Wide DNA Methylation of Colorectal Cancer Metastasis

“…GO analysis showed that shared hypermethylated genes in primary tumour and LNM were mainly related to synaptic and neural activity. Interestingly, these biological processes have been previously associated with CICs [ 43 , 44 ]. In addition, we found enrichment of other biological processes, including mesenchymal development, tissue morphogenesis and stem cell differentiation, which are known mechanisms for EMT and metastasis [ 45 ].…”

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

“…Compared to non-CSCs, CSCs are distinct for their immune resistance, and cancer immunosurveillance enhances certain populations of cancer cells with stem-like characteristics. For CSCs to maintain the tumorigenic process, CSC immune evasion is essential, including elevated PD-L1 expression [224,225]. In addition to immune evasion, CSCs display plasticity in terms of favorable DNA repair pathways in response to genotoxic-mediated DNA damage.…”

“…Standard cancer therapies often fail due to the generation of CSCs, with signaling pathways like Wnt, Hedgehog, Notch, hypoxia and PI3K/AKT/mTOR being aberrantly regulated in these cells [225][226][227]. These signaling pathways are also involved directly or indirectly with resistance to topo-active drugs in cancer cells [33].…”