Department of Obstetrics and Gynecology, Tri-service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
Department of Medical Research and Education, Cheng-Hsin Hospital, Taipei 112, Taiwan.
Int J Mol Sci. 2018 Oct 24;19(11):3311. doi: 10.3390/ijms19113311.
Serous carcinoma (SC) is the most common and lethal subtype of epithelial ovarian carcinoma; immunotherapy is a potential treatment for SC, however, the global immunological functions of SC as well as their change during the progression of SC have not been investigated in detail till now. We conducted a genome-wide integrative analysis to investigate the immunofunctionomes of SC at four tumor stages by quantifying the immunological functions defined by the Gene Ontology gene sets. DNA microarray gene expression profiles of 1100 SCs and 136 normal ovarian tissue controls were downloaded from the Gene Expression Omnibus database and converted to the functionome. Then the immunofunctionomes were reconstructed by extracting the offspring from the functionome for the four SC staging groups. The key immunological functions extracted from immunofunctionomes with a series of filters revealed that the immunopathy of SC consisted of a group of deregulated functions with the core members including B cell activation and differentiation, regulation of leukocyte chemotaxis/cellular extravasation, antigen receptor mediated signaling pathway, T helper mediated immunity and macrophage activation; and the auxiliary elements included leukocyte mediated immunity, regulation of inflammatory response, T cell differentiation, mononuclear cell migration, megakaryocyte differentiation, complement activation and cytokine production. These deregulated immunological functions reveal the candidates to target in the immunotherapy.
浆液性癌 (SC) 是上皮性卵巢癌中最常见和最致命的亚型;免疫疗法是治疗 SC 的一种潜在方法,然而,SC 的全球免疫学功能及其在 SC 进展过程中的变化至今尚未详细研究。我们通过定量定义为基因本体论基因集的免疫学功能,进行了全基因组综合分析,以研究四个肿瘤阶段的 SC 的免疫功能组。从基因表达综合数据库中下载了 1100 个 SC 和 136 个正常卵巢组织对照的 DNA 微阵列基因表达谱,并转换为功能组。然后,通过从四个 SC 分期组的功能组中提取后代来重建免疫功能组。通过一系列筛选从免疫功能组中提取的关键免疫学功能表明,SC 的免疫病理学由一组失调的功能组成,核心成员包括 B 细胞激活和分化、白细胞趋化/细胞外渗的调节、抗原受体介导的信号通路、T 辅助介导的免疫和巨噬细胞激活;辅助元素包括白细胞介导的免疫、炎症反应的调节、T 细胞分化、单核细胞迁移、巨核细胞分化、补体激活和细胞因子产生。这些失调的免疫学功能揭示了免疫治疗中的候选靶点。