Department of Hematology, The Second Affiliated Hospital of Dalian Medical University, Liaoning, Dalian, People's Republic of China.
Department of Pathology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
Sci Rep. 2022 Jul 1;12(1):11161. doi: 10.1038/s41598-022-15205-7.
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.
拓扑异构酶 IIα（TOP2A）在多种肿瘤类型中发挥致癌作用。然而，目前尚无关于 TOP2A 功能和上游分子机制的泛癌症分析。我们首次通过癌症基因组图谱（TCGA）数据库分析了 TOP2A 在 33 种癌症类型中的潜在致癌作用。TOP2A 的过表达存在于几乎所有的癌症类型中，并且在大多数情况下与预后不良和晚期病理阶段有关。此外，在几种癌症类型中观察到 TOP2A 遗传改变的高频，并且在某些情况下与预后有关。此外，我们还对 TOP2A 的上游 miRNAs 和 lncRNAs 进行了分析，在肾透明细胞癌（SNHG3-miR-139-5p）、肾乳头状细胞癌（TMEM147-AS1/N4BP2L2-IT2/THUMPD3-AS1/ERICD/TTN-AS1/SH3BP5-AS1/THRB-IT1/SNHG3/NEAT1-miR-139-5p）、肝肝细胞癌（SNHG3/THUMPD3-AS1/NUTM2B-AS1/NUTM2A-AS1-miR-139-5p 和 SNHG6/GSEC/SNHG1/SNHG14/LINC00265/MIR3142HG-miR-101-3p）和肺腺癌（TYMSOS/HELLPAR/SNHG1/GSEC/SNHG6-miR-101-3p）中建立了 ceRNA 网络。在大多数癌症类型中，TOP2A 的表达通常与癌症相关成纤维细胞、M0 和 M1 巨噬细胞呈正相关。此外，TOP2A 与大多数癌症类型中免疫检查点（CD274、CTLA4、HAVCR2、LAG3、PDCD1 和 TIGIT）的表达呈正相关。我们的第一项 TOP2A 泛癌症研究有助于了解不同癌症中 TOP2A 的预后作用、免疫作用和潜在的上游分子机制。
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