Integrative Analysis to Identify Genes Associated with Stemness and Immune Infiltration in Glioblastoma

Abstract

It is imperative to identify the mechanisms that confer stemness to the cancer cells for more effective targeting. Moreover, there are not many studies on the link between stemness characteristics and the immune response in tumours. Therefore, in the current study involving GBM, we started with the study of BIRC5 (one of the rare genes differentially expressed in normal and cancer cells) and CXCR4 (gene involved in the survival and proliferation of CSCs). Together, these genes have not been systematically explored. We used a set of 27 promoter methylated regions in GBM. Our analysis showed that four genes corresponding to these regions, namely EOMES, BDNF, HLA-A, and PECAM1, were involved with BIRC5 and CXCR4. Interestingly, we found EOMES to be very significantly involved in stemness and immunology and it was positively correlated to CXCR4. Additionally, BDNF, which was significant in methylation, was negatively correlated to BIRC5.

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

“…The system here works towards simply killing the root cause and doesn't take into consideration the interactome around the tumor cells that is responsible for the progression of the cancer. Given the recently developed role of epigenetics in stem cell differentiation [244,245], transcription factors like Sox-2 [246,247], Oct-4 [248,249], Nanog [92,250], CXC-R4 [244,245], survivin (Birc5) [251][252][253], nestin [254], and Klf-4 [255] and their co-expression [255][256][257][258] are also promising avenues through which to capacitate efficacious therapy [91,259]. When considering CSCs as the point of attack within the TME-wherein targeting CSCs via microenvironment subsections of hypoxia, vasculature, and cellular components such as TAMs or CAFs is prevalent [67, 260]-a far more potent approach would be to target the stem cell pathways that imbue these cells with the properties of plasticity, heterogeneity, and increased proliferation, which are answerable to ineffective treatment.…”

Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response

“…The survivin gene Baculoviral IAP Repeat (BIR) Containing 5 (BIRC5) shows very little expression in normal adult differentiated tissues. Most cancers that show an increased expression of survivin are often associated with poor prognosis [ 15 , 16 , 17 ]. It is involved in signaling pathways, including but not limited to PI3K/AKT, JAK/STAT, WNT/β-Catenin, TGF-β, SMAD, NF-κB and NOTCH, in a variety of cancers [ 18 ].…”

“…It is involved in signaling pathways, including but not limited to PI3K/AKT, JAK/STAT, WNT/β-Catenin, TGF-β, SMAD, NF-κB and NOTCH, in a variety of cancers [ 18 ]. Studies have reported the overexpression of this gene in GBM, where it mediates cell growth and maintenance, apoptosis, invasiveness, vascularization and therapy resistance and hence indicators of poor prognosis [ 16 , 19 , 20 , 21 ].…”