Identification of potential biomarkers and candidate small molecule drugs in glioblastoma

Abstract

Background and aims: Glioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor. This study aimed to identify the key genes associated with the development of GBM and provide new diagnostic and therapies for GBM. Methods: Three microarray datasets (GSE111260, GSE103227, and GSE104267) were selected from Gene Expression Omnibus (GEO) database for integrated analysis. The differential expressed genes (DEGs) between GBM and normal tissues were identified. Then, prognosis-related DEGs were screened by survival analysis, followed by functional enrichment analysis. The protein-protein interaction (PPI) network was constructed to explore the hub genes associated with GBM. The mRNA and protein expression levels of hub genes were respectively validated in silico using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. Subsequently, the small molecule drugs of GBM were predicted by using Connectivity Map (CMAP) database. Results: A total of 78 prognosis-related DEGs were identified, of which10 hub genes with higher degree were obtained by PPI analysis. The mRNA expression and protein expression levels of CETN2, MKI67, ARL13B, and SETDB1 were overexpressed in GBM tissues, while the expression levels of CALN1, ELAVL3, ADCY3, SYN2, SLC12A5, and SOD1 were down-regulated in GBM tissues. Additionally, these genes were significantly associated with the prognosis of GBM. We eventually predicted the 10 most vital small molecule drugs, which potentially imitate or reverse GBM carcinogenic status. Cycloserine and 11-deoxy-16,16-dimethylprostaglandin E2 might be considered as potential therapeutic drugs of GBM. Conclusions: Our study provided 10 key genes for diagnosis, prognosis, and therapy for GBM. These findings might contribute to a better comprehension of molecular mechanisms of GBM development, and provide new perspective for further GBM research. However, specific regulatory mechanism of these genes needed further elaboration.

DNA Damage Repair-Related Genes Signature for Immune Infiltration and Outcome in Cervical Cancer

“…Studies ( Mullee and Morrison, 2016 ; Semer et al, 2019 ) had shown that CEN2 was a transcriptional co activator, which could reshape the epigenetic landscape of promoters. In previous cancer research, it had received some attention as a potential biomarker ( Anurag et al, 2018 ; Lu et al, 2020 ).…”

Centrin 2: A Novel Marker of Mature and Neoplastic Human Astrocytes

“…Our results demonstrate that CETN2 is expressed in astrocytes of primary glioblastomas, in a stage of tumor progression which is, by definition, the most severe. Lu et al (2020) also reported that low CETN2 expression could be correlated to better survival of patients with GBM, thus suggesting that CETN2 expression increases with disease evolution. However, a more systematic investigation on lower grade astrocytomas would be needed to validate this hypothesis.…”

“…In GBM, channels involved in ionic transport have their expression frequently affected (Polisetty et al, 2012) and calcium concentration, in particular, has been demonstrated to be pivotal for tumor initiation, maintenance, and infiltration (Leclerc et al, 2016;Guan et al, 2018). Accordingly, the transcriptional profile of several genes coding for calcium-binding proteins, including CETN2, have their expression altered in GBM (Loh et al, 2010(Loh et al, , 2012Robil et al, 2015;Lu et al, 2020). Our results demonstrate that CETN2 is expressed in astrocytes of primary glioblastomas, in a stage of tumor progression which is, by definition, the most severe.…”

“…Several centrosomal genes have also been reported to have an abnormal expression in brain tumors. Among these, CETN2 mRNA has been described to be overexpressed in astrocytomas and in its most aggressive form, GBM (Loh et al, 2010(Loh et al, , 2012Lu et al, 2020). However, at present, no indications have been provided to describe CETN2 cellular localization in neoplastic tissue.…”

Post‐translational modifications of histones: Mechanisms, biological functions, and therapeutic targets

“…found that the changes in gene expression of various methyltransferases, acetyltransferases, and deacetylases promoted the pathogenesis of GBM 189 . The nuclear expression levels of lysine methyltransferases SETDB1, KMT5B, Suv‐39h1, and EZH2 in GBM are up‐regulated, compared with normal tissues, and correlated with advanced histological grades 190–193 . Besides, the inhibition of LSD1 in GBM has been discovered by Chandra et al.…”