Oncogenic role and potential regulatory mechanism of topoisomerase IIα in a pan-cancer analysis.

Topoisomerase IIα (TOP2A) plays an oncogenic role in multiple tumor types. However, no pan-cancer analysis about the function and the upstream molecular mechanism of TOP2A is available. For the first time, we analyzed potential oncogenic roles of TOP2A in 33 cancer types via The Cancer Genome Atlas (TCGA) database. Overexpression of TOP2A was existed in almost all cancer types, and related to poor prognosis and advanced pathological stages in most cases. Besides, the high frequency of TOP2A genetic alterations was observed in several cancer types, and related to prognosis in some cases. Moreover, we conduct upstream miRNAs and lncRNAs of TOP2A to establish ceRNA networks in kidney renal clear cell carcinoma (SNHG3-miR-139-5p), kidney renal papillary cell carcinoma (TMEM147-AS1/N4BP2L2-IT2/THUMPD3-AS1/ERICD/TTN-AS1/SH3BP5-AS1/THRB-IT1/SNHG3/NEAT1-miR-139-5p), liver hepatocellular carcinoma (SNHG3/THUMPD3-AS1/NUTM2B-AS1/NUTM2A-AS1-miR-139-5p and SNHG6/GSEC/SNHG1/SNHG14/LINC00265/MIR3142HG-miR-101-3p) and lung adenocarcinoma (TYMSOS/HELLPAR/SNHG1/GSEC/SNHG6-miR-101-3p). TOP2A expression was generally positively correlated with cancer associated fibroblasts, M0 and M1 macrophages in most cancer types. Furthermore, TOP2A was positively associated with expression of immune checkpoints (CD274, CTLA4, HAVCR2, LAG3, PDCD1 and TIGIT) in most cancer types. Our first TOP2A pan-cancer study contributes to understanding the prognostic roles, immunological roles and potential upstream molecular mechanism of TOP2A in different cancers.