Chen Zhenyue, Jiang Weiyi, Li Zhen, Zong Yun, Deng Gaopi
The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Oncol. 2022 May 12;12:877369. doi: 10.3389/fonc.2022.877369. eCollection 2022.
Ovarian cancer (OV) is a complex gynecological disease, and its molecular characteristics are not clear. In this study, the molecular characteristics of OV subtypes based on metabolic genes were explored through the comprehensive analysis of genomic data. A set of transcriptome data of 2752 known metabolic genes was used as a seed for performing non negative matrix factorization (NMF) clustering. Three subtypes of OV (C1, C2 and C3) were found in analysis. The proportion of various immune cells in C1 was higher than that in C2 and C3 subtypes. The expression level of immune checkpoint genes TNFRSF9 in C1 was higher than that of other subtypes. The activation scores of cell cycle, RTK-RAS, Wnt and angiogenesis pathway and ESTIMATE immune scores in C1 group were higher than those in C2 and C3 groups. In the validation set, grade was significantly correlated with OV subtype C1. Functional analysis showed that the extracellular matrix related items in C1 subtype were significantly different from other subtypes. Drug sensitivity analysis showed that C2 subtype was more sensitive to immunotherapy. Survival analysis of differential genes showed that the expression of PXDN and CXCL11 was significantly correlated with survival. The results of tissue microarray immunohistochemistry showed that the expression of PXDN was significantly correlated with tumor size and pathological grade. Based on the genomics of metabolic genes, a new OV typing method was developed, which improved our understanding of the molecular characteristics of human OV.
卵巢癌（OV）是一种复杂的妇科疾病，其分子特征尚不清楚。在本研究中，通过对基因组数据的综合分析，探索了基于代谢基因的OV亚型的分子特征。一组2752个已知代谢基因的转录组数据被用作进行非负矩阵分解（NMF）聚类的种子。分析中发现了三种OV亚型（C1、C2和C3）。C1中各种免疫细胞的比例高于C2和C3亚型。C1中免疫检查点基因TNFRSF9的表达水平高于其他亚型。C1组细胞周期、RTK-RAS、Wnt和血管生成途径的激活评分以及ESTIMATE免疫评分高于C2和C3组。在验证集中，分级与OV亚型C1显著相关。功能分析表明，C1亚型中与细胞外基质相关的项目与其他亚型有显著差异。药物敏感性分析表明，C2亚型对免疫治疗更敏感。差异基因的生存分析表明，PXDN和CXCL11的表达与生存显著相关。组织芯片免疫组化结果表明，PXDN的表达与肿瘤大小和病理分级显著相关。基于代谢基因的基因组学，开发了一种新的OV分型方法，这提高了我们对人类OV分子特征的理解。
