Analyses of metastasis-associated genes in IDH wild-type glioma

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RESEARCH ARTICLE

Open Access

Analyses of metastasis-associated genes in IDH wild-type glioma Xiaozhi Li1 and Yutong Meng2*

Abstract Background: Glioma is the most common malignant tumor of the brain. The existence of metastatic tumor cells is an important cause of recurrence even after radical glioma resection. Methods: Single-cell sequencing data and high-throughput data were downloaded from GEO database and TCGA/ CGGA database. By means of PCA and tSNE clustering methods, metastasis-associated genes in glioma were identified. GSEA explored possible biological functions that these metastasis-associated genes may participate in. Univariate and multivariate Cox regression were used to construct a prognostic model. Results: Glioma metastatic cells and metastasis-associated genes were identified. The prognostic model based on metastasis-associated genes had good sensitivity and specificity for the prognosis of glioma. These genes may be involved in signal pathways such as cellular protein catabolic process, p53 signaling pathway, transcriptional misregulation in cancer and JAK-STAT signaling pathway. Conclusion: This study explored glioma metastasis-associated genes through single-cell sequencing data mining, and aimed to identify prognostic metastasis-associated signatures for glioma and may provide potential targets for further cancer research. Keywords: Glioma, Metastasis, Prognosis, Invasion, Single-cell sequencing

Background Glioma is the most common malignant tumor in the brain. In recent years, research on glioma especially on the molecular mechanisms has been increasing. In 2016, the World Health Organization first applied histology and molecular classification to define central nervous system tumors simultaneously [1]. Although with the continuous improvement of glioma diagnosis and treatment technology, the 5-year survival rate of patients with grade IV glioma is less than 5% [2], and the median survival time is about 12–15 months [3]. Glioma is composed of the tumor core and metastatic tumor cells. The metastatic tumor cells can be located a few * Correspondence: [email protected] 2 Department of Stomatology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang, Liaoning Province 110004, People’s Republic of China Full list of author information is available at the end of the article

centimeters away from the tumor core area. The existence of metastatic tumor cells is an important cause of recurrence even after radical glioma resection [4]. The process of tumor metastasis is generally considered to be divided into the following four steps: (1) separating of invading cells from the primary site; (2) adhesion to the extracellular matrix: (3) degradation of the extracellular matrix; (4) movement of the invasive cells [5, 6]. In addition, the heterogeneity of the cells within the tumor also promotes the metastatic capacity of the tumor cells. However, specific molecular mechanism of the metastasis of glioma is still unclear. Traditional high-throughput sequencing data analysis is