Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China.
Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
PLoS One. 2022 Oct 26;17(10):e0274546. doi: 10.1371/journal.pone.0274546. eCollection 2022.
Topoisomerases are nuclear enzymes that get to the bottom of topological troubles related with DNA all through a range of genetic procedures. More and more studies have shown that topoisomerase-mediated DNA cleavage plays crucial roles in tumor cell death and carcinogenesis. There is however still a lack of comprehensive multi-omics studies related to topoisomerase family genes from a pan-cancer perspective.
In this study, a multiomics pan-cancer analysis of topoisomerase family genes was conducted by integrating over 10,000 multi-dimensional cancer genomic data across 33 cancer types from The Cancer Genome Atlas (TCGA), 481 small molecule drug response data from cancer therapeutics response portal (CTRP) as well as normal tissue data from Genotype-Tissue Expression (GTEx). Finally, overall activity-level analyses of topoisomerase in pan-cancers were performed by gene set variation analysis (GSVA), together with differential expression, clinical relevancy, immune cell infiltration and regulation of cancer-related pathways.
Dysregulated gene expression of topoisomerase family were related to genomic changes and abnormal epigenetic modifications. The expression levels of topoisomerase family genes could significantly impact cancer progression, intratumoral heterogeneity, alterations in the immunological condition and regulation of the cancer marker-related pathways, which in turn caused the differences in potential drugs sensitivity and the distinct prognosis of patients.
It was anticipated that topoisomerase family genes would become novel prognostic biomarkers for cancer patients and provide new insights for the diagnosis and treatment of tumors.
拓扑异构酶是核酶，通过一系列遗传过程，深入研究与 DNA 相关的拓扑问题。越来越多的研究表明，拓扑异构酶介导的 DNA 断裂在肿瘤细胞死亡和致癌作用中起着关键作用。然而，从泛癌的角度来看，仍然缺乏关于拓扑异构酶家族基因的综合多组学研究。
本研究通过整合来自癌症基因组图谱（TCGA）的 33 种癌症类型的超过 10000 个多维癌症基因组数据、癌症治疗反应门户（CTRP）的 481 种小分子药物反应数据以及基因型-组织表达（GTEx）的正常组织数据，对拓扑异构酶家族基因进行了泛癌多组学分析。最后，通过基因集变异分析（GSVA）对泛癌中的拓扑异构酶进行整体活性水平分析，同时进行差异表达、临床相关性、免疫细胞浸润和癌症相关途径的调控分析。
拓扑异构酶家族基因的失调表达与基因组变化和异常表观遗传修饰有关。拓扑异构酶家族基因的表达水平可显著影响癌症的进展、肿瘤内异质性、免疫状态的改变和癌症标志物相关途径的调控，进而导致潜在药物敏感性的差异和患者预后的不同。
预计拓扑异构酶家族基因将成为癌症患者新的预后生物标志物，并为肿瘤的诊断和治疗提供新的见解。
