Novel Biomarker Genes for Prognosis of Survival and Treatment of Glioma

Xiaopeng Zhu; Sian Pan; Rui Li; Zebo Chen; Xingyun Xie; Deqing Han; Shengqing Lv; Yongkai Huang

doi:10.3389/fonc.2021.667884

Novel Biomarker Genes for Prognosis of Survival and Treatment of Glioma

Front Oncol. 2021 Dec 15:11:667884. doi: 10.3389/fonc.2021.667884. eCollection 2021.

Authors

Xiaopeng Zhu¹, Sian Pan², Rui Li³, Zebo Chen¹, Xingyun Xie¹, Deqing Han¹, Shengqing Lv⁴, Yongkai Huang¹

Affiliations

¹ Department of Neurosurgery, Zhuzhou Central Hospital, Zhuzhou, China.
² Department of Rehabilitation Medicine, Zhuzhou Central Hospital, Zhuzhou, China.
³ Department of Operating Theatre, Zhuzhou Central Hospital, Zhuzhou, China.
⁴ Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

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.

Keywords: GEO; TMB; chemotherapy; glioblastoma; immunotherapy; prognosis; radiotherapy.