Identification and Validation of Prognostic Markers for Endometriosis-Associated Ovarian Cancer.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials Pub Date : 2024-07-22 eCollection Date: 2024-01-01 DOI:10.7150/ijms.97024
Huilin Yang, Yue Deng, Ying Dong, Yiqun Ma, Lihua Yang
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引用次数: 0

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

子宫内膜异位症相关卵巢癌预后标志物的鉴定与验证
背景: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)的风险因素。我们的目的是鉴定和验证与子宫内膜异位症相关的基因特征,这些特征可作为评估 EAOC 患者预后的潜在生物标志物。研究方法EMs和对照样本的数据来自GEO数据库。加权基因共表达网络分析(WGCNA)发现了与EMs显著相关的模块化基因。此外,还进行了KEGG通路和GO功能富集分析。通过单变量 Cox 回归分析,筛选出与 EAOC 患者预后相关的标记基因。最后,通过 RT-qPCR 和免疫组化验证了 ADAMTS19 和 TUBB 在正常卵巢和 EAOC 组织中的表达,并通过 CCK8 和 Transwell 试验初步探讨了 ADAMTS19 和 TUBB 的生物学功能。结果通过对 EAOC 数据集的分析,WGCNA 发现了 2 个共表达模块,共包括 615 个基因,并检测到 7642 个差异表达基因(DEG)。在对 615 个模块基因和 7642 个 DEGs 进行交叉分析后,得到了 214 个共享基因,并通过单变量 COX 回归分析发现了 10 个与 EAOC 预后相关的基因。此外,RT-qPCR和免疫组化染色实验表明,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,细胞实验显示 ADAMTS19 促进了 EAOC 细胞的增殖和侵袭,而 TUBB 的过表达则抑制了这些过程。结论本研究发现并验证了新的EMs相关基因标记,这些标记可作为评估EAOC患者预后风险的潜在生物标记。此外,其中一些基因可能具有新的治疗靶点的意义,可用于指导临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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