Expression and clinical significance of TIMELESS in glioma

In recent years, studies have shown that TIMELESS, as an oncogene, is involved in progression of cancers. However, its relationship with prognosis in glioma patients is rarely reported. Our purpose was to explore the role of TIMELESS in glioma. Based on 1814 glioma samples from multiple databases such as The Cancer Genome Atlas (TCGA), The Chinese Glioma Genome Atlas (CGGA), and The Gene Expression Omnibus (GEO), we use a variety of bioinformatics methods to verify the mechanism of action of TIMELESS in glioma from mRNA to protein, from appearance to mechanism analysis, from clinical features to prognosis. Then, the connectivity map (CMap) tool was used to predict drugs that inhibit the expression of TIMELESS. First, we found TIMELESS is highly expressed in glioma at mRNA and protein levels. Second, TIMELESS is an independent risk factor in prognosis and has suitable clinical diagnostic value in glioma. It was also positively correlated with World Health Organization (WHO) grade, age, and histology, and negatively correlated with isocitrate dehydrogenase (IDH) 1 mutation and 1p19q codeletion. Third, base excision, cell cycle, and mismatch repair pathway were activated by TIMELESS in glioma. We predict small molecules to inhibit TIMELESS such as 8-azaguanine, gw8510, 6-thioguanosine, and ursodeoxycholic acid. This study is the first comprehensive analysis of TIMELESS, revealing a relationship between this novel oncogene, clinical characteristics of patients with glioma, and a mechanism leading to poor prognosis. It also provides a biomarker for diagnosis and treatment of glioma and reveal the pathologic progress of glioma at the genetic level.