Abstract
BackgroundGliomas are the most common and malignant brain tumors. The standard therapy is surgery combined with radiotherapy, chemotherapy, and/or other comprehensive methods. However, the emergence of chemoresistance is the main obstacle in treatment and its mechanism is still unclear.MethodsWe firstly developed a multi-gene signature by integrated analysis of cancer stem cell and drug resistance related genes. The Chinese Glioma Genome Atlas (CGGA, 325 samples) and The Cancer Genome Atlas (TCGA, 699 samples) datasets were then employed to verify the efficacy of the risk signature and investigate its significance in glioma prognosis. GraphPad Prism, SPSS and R language were used for statistical analysis and graphical work.ResultsThis signature could distinguish the prognosis of patients, and patients with high risk score exhibited short survival time. The Cox regression and Nomogram model indicated the independent prognostic performance and high prognostic accuracy of the signature for survival. Combined with a well-known chemotherapy impact factor-MGMT promoter methylation status, this risk signature could further subdivide patients with distinct survival. Functional analysis of associated genes revealed signature-related biological process of cell proliferation, immune response and cell stemness. These mechanisms were confirmed in patient samples.ConclusionsThe signature was an independent and powerful prognostic biomarker in glioma, which would improve risk stratification and provide a more accurate assessment of personalized treatment.1f-pc3KNkXFCvWW6HffFRoAdditional file 8 Video abstract
Highlights
Gliomas are the most common and malignant brain tumors
The same analysis was applied in COSMIC dataset to reveal the TMZ drug resistant (TMZ-DR) genes according to the half maximal inhibitory concentration (IC50)
Our results demonstrated a tight connection between the risk score and Tim3/B7H3 (Fig. 7a-b), which may partly explain the poor prognosis of patients and provide some clues for potential immunotherapy
Summary
Gliomas are the most common and malignant brain tumors. The standard therapy is surgery combined with radiotherapy, chemotherapy, and/or other comprehensive methods. Glioma is the most common primary malignant tumors of the central nervous system, accounting for 30% of all brain tumors and 80% of all malignant brain tumors [1]. It is one of the representative malignant tumors with the characteristics of strong genetic heterogeneity, high mortality and chemotherapy resistance. Researchers have found the relationship between cancer stem cells (CSCs) and drug resistance. We focused on TMZ therapy, CSCs and diverse related oncogenic drivers within patients by high throughput sequencing method and established gene signature, a statistical model including several biomarkers, to predict the prognosis and chemoresistance of glioma patients [7,8,9]
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