Yang Huilin, Deng Yue, Dong Ying, Ma Yiqun, Yang Lihua
Department of Gynecology, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, China.
Int J Med Sci. 2024 Jul 22;21(10):1903-1914. doi: 10.7150/ijms.97024. eCollection 2024.
Growing evidence suggests that endometriosis (EMs) is a risk factor for endometriosis-associated ovarian cancer (EAOC). The aim was to identify and validate gene signatures associated with EMs that may serve as potential biomarkers for evaluating the prognosis of patients with EAOC. The data of EMs and control samples was obtained from GEO database. The weighted gene co-expression network analysis (WGCNA) identified modular genes significantly associated with EMs. The KEGG pathway and GO functional enrichment analyses were also performed. Univariate Cox regression analysis was conducted to screen marker genes associated with the prognosis of EAOC patients. Finally, RT-qPCR and immunohistochemical verified the expression of ADAMTS19 and TUBB in normal ovarian and EAOC tissues, and the biological functions of ADAMTS19 and TUBB were preliminarily explored by CCK8 and Transwell assays. The WGCNA identified 2 co-expression modules, which in total included 615 genes, and 7642 differentially expressed genes (DEGs) were detected thorough analysis of the EAOC dataset. After taking the intersection of 615 modular genes and 7642 DEGs, 214 shared genes were obtained, and univariate COX regression analysis pointed 10 genes associated with the prognosis of EAOC. Moreover, it was demonstrated by RT-qPCR and immunohistochemical staining experiments that ADAMTS19 expression was elevated, while TUBB expression was reduced in EAOC compared with normal ovarian cells and tissues. Finally, cell experiments revealed that ADAMTS19 promoted the proliferation and invasion in EAOC cells, while overexpression of TUBB inhibited these processes. The present study identified and validated new EMs-associated gene markers, which could serve as potential biomarkers for assessing the prognostic risk of EAOC patients. In addition, some of these genes may have significance as novel therapeutic targets and could be used to guide clinical applications.
越来越多的证据表明，子宫内膜异位症（EMs）是子宫内膜异位症相关卵巢癌（EAOC）的一个风险因素。目的是识别并验证与EMs相关的基因特征，这些特征可作为评估EAOC患者预后的潜在生物标志物。EMs和对照样本的数据从基因表达综合数据库（GEO数据库）获得。加权基因共表达网络分析（WGCNA）确定了与EMs显著相关的模块基因。还进行了京都基因与基因组百科全书（KEGG）通路和基因本体（GO）功能富集分析。进行单因素Cox回归分析以筛选与EAOC患者预后相关的标记基因。最后，实时定量聚合酶链反应（RT-qPCR）和免疫组织化学验证了去整合素样金属蛋白酶19（ADAMTS19）和微管蛋白β（TUBB）在正常卵巢组织和EAOC组织中的表达，并通过细胞计数试剂盒8（CCK8）和Transwell实验初步探索了ADAMTS19和TUBB的生物学功能。WGCNA识别出2个共表达模块，总共包含615个基因，通过对EAOC数据集的全面分析检测到7642个差异表达基因（DEG）。在615个模块基因和7642个DEG取交集后，获得了214个共享基因，单因素COX回归分析指出了10个与EAOC预后相关的基因。此外，RT-qPCR和免疫组织化学染色实验表明，与正常卵巢细胞和组织相比，EAOC中ADAMTS19表达升高，而TUBB表达降低。最后，细胞实验表明，ADAMTS19促进EAOC细胞的增殖和侵袭，而TUBB的过表达抑制了这些过程。本研究识别并验证了新的与EMs相关的基因标记，这些标记可作为评估EAOC患者预后风险的潜在生物标志物。此外，其中一些基因可能作为新的治疗靶点具有重要意义，并可用于指导临床应用。
