Abstract
Glioma is the common histological subtype of malignancy in the central nervous system, with high morbidity and mortality. Glioma cancer stem cells (CSCs) play essential roles in tumor recurrence and treatment resistance. Thus, exploring the stem cell-related genes and subtypes in glioma is important. In this study, we collected the RNA-sequencing (RNA-seq) data and clinical information of glioma patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. With the differentially expressed genes (DEGs) and weighted gene correlation network analysis (WGCNA), we identified 86 mRNA expression-based stemness index (mRNAsi)-related genes in 583 samples from TCGA RNA-seq dataset. Furthermore, these samples from TCGA database could be divided into two significantly different subtypes with different prognoses based on the mRNAsi corresponding gene, which could also be validated in the CGGA database. The clinical characteristics and immune cell infiltrate distribution of the two stemness subtypes are different. Then, functional enrichment analyses were performed to identify the different gene ontology (GO) terms and pathways in the two different subtypes. Moreover, we constructed a stemness subtype-related risk score model and nomogram to predict the prognosis of glioma patients. Finally, we selected one gene (ETV2) from the risk score model for experimental validation. The results showed that ETV2 can contribute to the invasion, migration, and epithelial-mesenchymal transition (EMT) process of glioma. In conclusion, we identified two distinct molecular subtypes and potential therapeutic targets of glioma, which could provide new insights for the development of precision diagnosis and prognostic prediction for glioma patients.
Highlights
Gliomas are the most common primary malignant tumor of the central nervous system (Ostrom et al, 2014)
The mRNAsi and Clinical Characteristics in Glioma mRNA expression-based stemness index is a useful indicator that can estimate the number of cancer stem cells (CSCs) by assessing the similarity and heterogeneity between the tumor cells and stem cells
There was no significant difference of mRNAsi between normal and tumor samples (Figure 2A)
Summary
Gliomas are the most common primary malignant tumor of the central nervous system (Ostrom et al, 2014). Exploring the molecular mechanism of glioma may facilitate the identification of prognostic biomarkers and potential targets for the treatment of glioma. The mRNA expressionbased stemness index (mRNAsi), which represents the transcriptomic stemness expression, has been applied to assess CSC characteristics (Malta et al, 2018). In some cancers, such as bladder, lung, breast, or endometrial carcinoma, it has been reported that mRNAsi is a credible marker and is associated with tumor stage (Pan et al, 2019; Liu et al, 2020; Pei et al, 2020).
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