Overexpressed XRCC2 as an independent risk factor for poor prognosis in glioma patients

Abstract

Background: XRCC2, a homologous recombination-related gene, has been reported to be associated with a variety of cancers. However, its role in glioma has not been reported. This study aimed to find out the role of XRCC2 in glioma and reveal in which glioma-specific biological processes is XRCC2 involved based on thousands of glioma samples, thereby, providing a new perspective in the treatment and prognostic evaluation of glioma. Methods: The expression characteristics of XRCC2 in thousands of glioma samples from CGGA and TCGA databases were comprehensively analyzed. Wilcox or Kruskal test was used to analyze the expression pattern of XRCC2 in gliomas with different clinical and molecular features. The effect of XRCC2 on the prognosis of glioma patients was explored by Kaplan–Meier and Cox regression. Gene set enrichment analysis (GSEA) revealed the possible cellular mechanisms involved in XRCC2 in glioma. Connectivity map (CMap) was used to screen small molecule drugs targeting XRCC2 and the expression levels of XRCC2 were verified in glioma cells and tissues by RT-qPCR and immunohistochemical staining. Results: We found the overexpression of XRCC2 in glioma. Moreover, the overexpressed XRCC2 was associated with a variety of clinical features related to prognosis. Cox and meta-analyses showed that XRCC2 is an independent risk factor for the poor prognosis of glioma. Furthermore, the results of GSEA indicated that overexpressed XRCC2 could promote malignant progression through involved signaling pathways, such as in the cell cycle. Finally, doxazosin, quinostatin, canavanine, and chrysin were identified to exert anti-glioma effects by targeting XRCC2. Conclusions: This study analyzed the expression pattern of XRCC2 in gliomas and its relationship with prognosis using multiple datasets. This is the first study to show that XRCC2, a novel oncogene, is significantly overexpressed in glioma and can lead to poor prognosis in glioma patients. XRCC2 could serve as a new biomarker for glioma diagnosis, treatment, and prognosis evaluation, thus bringing new insight into the management of glioma.