Zhu Xiaopeng, Pan Sian, Li Rui, Chen Zebo, Xie Xingyun, Han Deqing, Lv Shengqing, Huang Yongkai
Department of Neurosurgery, Zhuzhou Central Hospital, Zhuzhou, China.
Department of Rehabilitation Medicine, Zhuzhou Central Hospital, Zhuzhou, China.
Front Oncol. 2021 Dec 15;11:667884. doi: 10.3389/fonc.2021.667884. eCollection 2021.
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.
多形性胶质母细胞瘤（GBM）是最具侵袭性的原发性中枢神经系统恶性肿瘤。尽管有手术、放疗和化疗等治疗方法，但GBM的5年生存率仅为5.8%。因此，寻找GBM预后和治疗的新生物标志物势在必行。在本研究中，通过分析GSE12657、GSE90886和GSE90598数据集，共鉴定出GBM中141个差异表达基因（DEG）。在进行数据降维后，Kaplan-Meier生存分析表明，与正常组织相比，GBM组织中PTPRN和RIM-BP2的表达下调，且这些基因的表达是GBM的良好预后生物标志物（p<0.05）。然后，使用GSE46531数据集和癌症药物敏感性基因组学（GDSC）数据库来研究GBM的放疗（RT）和化疗敏感性与PTPRN和RIM-BP2表达之间的关系。PTPRN在放疗抵抗患者中的表达显著升高（p<0.05），但与替莫唑胺（TMZ）抵抗无关。RIM-BP2的表达水平与RT或TMZ治疗无关。在化疗药物中，顺铂和厄洛替尼对具有PTPRN或RIM-BP2表达的胶质瘤以及具有异柠檬酸脱氢酶（IDH）突变的低级别胶质瘤（LGG）具有显著良好的治疗效果（p<0.05）。低PTPRN表达组的肿瘤突变负荷（TMB）评分显著高于高PTPRN表达组（p=0.013），且肿瘤免疫细胞浸润程度较高。总之，这些发现有助于胶质瘤患者潜在生物标志物和治疗靶点的发现过程。
