依赖激素稳态的恶性肿瘤包括乳腺,子房,子宫颈,前列腺,睾丸和子宫肿瘤。激素参与协调过程的信号转导,如细胞凋亡,扩散,细胞周期或细胞骨架组织。目前,需要有助于有效诊断癌症的新型生物标志物。在这项研究中,研究了在激素敏感性癌变中重要的信号传导相关基因的预后意义.从FireBrowse收集了七个癌症队列的数据。通过MSig数据库浏览涉及特定途径的54个基因集。通过Monocle3评估概况,而通过PANTHER评估基因本体论。为了确认,使用WGCNA进行相关性分析。蛋白质-蛋白质网络通过Cytoscape和基因对生存的影响可视化,以及细胞周期或细胞骨架相关的预后特征,经过测试。确定了表达谱中的几个差异,他们中的一些人被允许区分组织学。功能注释揭示了细胞周期的各种调控,附着力,迁移,细胞凋亡和血管生成是这些差异的基础。临床特征,如组织学类型或癌症分期,是在评估模块-特征关系时发现的。在模块中,TopHub(COL6A3,TNR,GTF2A1,NKX3-1)直接与,例如,PDGFB,ITGA10、SP1或AKT3。在TopHubs和相互作用蛋白中,许多显示对风险比的影响,并影响细胞周期或细胞骨架相关的预后特征,例如,COL1A1或PDGFB。总之,这项研究通过鉴定证明细胞周期与细胞骨架之间存在串扰的基因,为进一步的激素敏感性癌变研究奠定了基础,为未来的治疗策略开辟了道路。
Malignancies dependent on hormone homeostasis include breast, ovary, cervical, prostate, testis and uterine tumors. Hormones are involved in signal transduction which orchestrate processes, such as apoptosis, proliferation, cell cycle or cytoskeleton organization. Currently, there is a need for novel biomarkers which would help to diagnose cancers efficiently. In this study, the genes implicated in signaling that is important in hormone-sensitive carcinogenesis were investigated regarding their prognostic significance. Data of seven cancer cohorts were collected from FireBrowse. 54 gene sets implicated in specific pathways were browsed through MSig database. Profiling was assessed via Monocle3, while gene ontology through PANTHER. For confirmation, correlation analysis was performed using WGCNA. Protein-protein networks were visualized via Cytoscape and impact of genes on survival, as well as cell cycle or cytoskeleton-related prognostic signatures, was tested. Several differences in expression profile were identified, some of them allowed to distinguish histology. Functional annotation revealed that various regulation of cell cycle, adhesion, migration, apoptosis and angiogenesis underlie these differences. Clinical traits, such as histological type or cancer staging, were found during evaluation of module-trait relationships. Of modules, the TopHubs (COL6A3, TNR, GTF2A1, NKX3-1) interacted directly with, e.g., PDGFB, ITGA10, SP1 or AKT3. Among TopHubs and interacting proteins, many showed an impact on hazard ratio and affected the cell cycle or cytoskeleton-related prognostic signatures, e.g., COL1A1 or PDGFB. In conclusion, this study laid the foundation for further hormone-sensitive carcinogenesis research through identification of genes which prove that crosstalk between cell cycle and cytoskeleton exists, opening avenues for future therapeutic strategies.