A Metabolic Plasticity-Based Signature for Molecular Classification and Prognosis of Lower-Grade Glioma

Abstract

Background: Glioma is one of the major health problems worldwide. Biomarkers for predicting the prognosis of Glioma are still needed. Methods: The transcriptome data and clinic information on Glioma were obtained from the CGGA, TCGA, GDC, and GEO databases. The immune infiltration status in the clusters was compared. The genes with differential expression were identified, and a prognostic model was developed. Several assays were used to detect RPH3A’s role in Glioma cells, including CCK-8, colony formation, wound healing, and transwell migration assay. Results: Lower Grade Glioma (LGG) was divided into two clusters. The immune infiltration difference was observed between the two clusters. We screened for genes that differed between the two groups. WGCNA was used to construct a co-expressed network using the DEGs, and four co-expressed modules were identified, which are blue, green, grey, and yellow modules. High-risk patients have a lower overall survival rate than low-risk patients. In addition, the risk score is associated with histological subtypes. Finally, the role of RPH3A was detected. The overexpression of RPH3A in LGG cells can significantly inhibit cell proliferation and migration and regulate EMT-regulated proteins. Conclusion: Our study developed a metabolic-related model for the prognosis of Glioma cells. RPH3A is a potential therapeutic target for Glioma.

Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas

“…In previous studies, astrocytoma patients demonstrated to experience the worst prognosis compared to other histology patients [ 36 , 37 , 38 ]. In addition, Xu et al and Yang et al found that the highest-risk scores were enriched in astrocytoma patients, but the lowest-risk scores were observed in oligodendroglioma patients [ 39 , 40 ]. These findings were similar to ours.…”

PSMB2 plays an oncogenic role in glioma and correlates to the immune microenvironment

“…Data for the study were collected from the TCGA database 15 ( https://www.cancer.gov/ccg/ ). We downloaded the data of glioma patients (n = 706) from TCGA ( http://portal.gdc.cancer.gov ) to analyze the RNA sequencing and patient information, and we used a transfer tool that was provided by GDC to capture the statistics 16 . In addition, we obtained data from the CGGA database ( http://www.cgga.org.cn/ ) to download PSMB2 expression and clinical data of glioma patients, and analyze the relationship between PSMB2 and patient prognosis.…”

Targeting GSTP1-dependent ferroptosis in lung cancer radiotherapy: Existing evidence and future directions

“…Further experiments demonstrated that downregulation of PCBP1 increased the sensitivity of head and neck cancer to ferroptosis (Lee et al, 2022). In addition, many other researchers found that radiotherapy might affect ferroptosis by mediating the expression of iron metabolism-related proteins such as iron ion-related carriers like ferritin, FPN, regulatory iron regulators, membrane iron transport auxiliary protein (Hephaestin) and copper cyanobacteria by mediating hypoxiainducible factor 1α (HIF-1α) or HIF-2α (Shah et al, 2009;Singhal et al, 2021;Yang et al, 2022). Therefore, we consider that the regulation of intracellular iron ion content by radiation to cause iron overload to enhance ferroptosis sensitivity in tumor cells is expected to be an effective way to enhance radiosensitivity.…”

“…Meanwhile, radiation is able to significantly increase the staining of C11-BODIPY, lipid peroxidation markers MDA and 4-HNE in cancer cells and tumor samples, indicating that radiation induces lipid peroxidation (Lei et al, 2020a;Zhang et al, 2021a;Zhou et al, 2022). Similarly, irradiated cells exhibit increased expression of the ferroptosis marker gene prostaglandin endoperoxide synthase 2 (PTGS2) (Busato et al, 2022;Yang et al, 2022). Furthermore, Seiji Torii et al shows that knockdown of Arachidonate 15-Lipoxygenase (ALOX15) decreases erastin-induced and RSL3-induced cellular ferroptosis, on the contrary exogenous overexpression of ALOX15 enhances the effects of these compounds.…”