Abstract
Glioblastoma multiforme (GBM) is the most aggressive malignant primary central nervous system tumor. Although surgery, radiotherapy, and chemotherapy treatments are available, the 5-year survival rate of GBM is only 5.8%. Therefore, it is imperative to find novel biomarker for the prognosis and treatment of GBM. In this study, a total of 141 differentially expressed genes (DEGs) in GBM were identified by analyzing the GSE12657, GSE90886, and GSE90598 datasets. After reducing the data dimensionality, Kaplan-Meier survival analysis indicated that expression of PTPRN and RIM-BP2 were downregulated in GBM tissues when compared with that of normal tissues and that the expression of these genes was a good prognostic biomarker for GBM (p<0.05). Then, the GSE46531 dataset and the Genomics of Drug Sensitivity in Cancer (GDSC) database were used to examine the relationship between sensitivity radiotherapy (RT) and chemotherapy for GBM and expression of PTPRN and RIM-BP2. The expression of PTPRN was significantly high in RT-resistant patients (p<0.05) but it was not related to temozolomide (TMZ) resistance. The expression level of RIM-BP2 was not associated with RT or TMZ treatment. Among the chemotherapeutic drugs, cisplatin and erlotinib had a significantly good treatment effect for glioma with expression of PTPRN or RIM-BP2 and in lower-grade glioma (LGG) with IDH mutation. (p < 0.05). The tumor mutational burden (TMB) score in the low PTPRN expression group was significantly higher than that in the high PTPRN expression group (p=0.013), with a large degree of tumor immune cell infiltration. In conclusion, these findings contributed to the discovery process of potential biomarkers and therapeutic targets for glioma patients.
Highlights
An estimated 86,010 new cases of primary brain and other central nervous system (CNS) tumors were diagnosed in the US in 2019 [1]
By normalizing and analyzing the GSE12657, GSE90886, and GSE90598 datasets, we identified 141 significantly overlapping differentially expressed genes (DEGs) in Glioblastoma multiforme (GBM)
By overlapping biomarkers derived from the LASSO algorithm and the Boruta algorithm, we obtained five GBM biomarkers
Summary
An estimated 86,010 new cases of primary brain and other central nervous system (CNS) tumors were diagnosed in the US in 2019 [1]. Novel Biomarker Genes approximately 15 months, and the 5-year survival rate is 5.8% [3]. In 2016, the updated World Health Organization (WHO) classification was the first to integrate molecular parameters with histology to define many tumor entities, including GBM [4], formulating a new concept for how GBM diagnoses should be structured in the molecular era. It is vital to develop appropriate and effective novel molecular signatures to improve survival and treatment response prediction for patients with GBM. Nlm.nih.gov/geo/), The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov), and Chinese Glioma Genome Atlas (CGGA, http://www.cgga.org.cn) provide us with the opportunity and resources to explore, integrate, and reanalyze the existing data for new GBM biomarker discovery Gene Expression Omnibus (GEO, https:// www.ncbi. nlm.nih.gov/geo/), The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov), and Chinese Glioma Genome Atlas (CGGA, http://www.cgga.org.cn) provide us with the opportunity and resources to explore, integrate, and reanalyze the existing data for new GBM biomarker discovery
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