Gumusoglu-Acar Ece, Gunel Tuba, Hosseini Mohammad Kazem, Dogan Berkcan, Tekarslan Efnan Elif, Gurdamar Berk, Cevik Nazife, Sezerman Ugur, Topuz Samet, Aydinli Kilic
Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, 34134 Istanbul, Turkey.
Department of Medical Genetics, Faculty of Medicine, Bursa Uludag University, 16059 Bursa, Turkey.
Oncol Lett. 2023 Feb 23;25(4):142. doi: 10.3892/ol.2023.13728. eCollection 2023 Apr.
Epithelial ovarian cancer (EOC) is the type of OC with the highest mortality rate. Due to the asymptomatic nature of the disease and few available diagnostic tests, it is mostly diagnosed at the advanced stage. Therefore, the present study aimed to discover predictive and/or early diagnostic novel circulating microRNAs (miRNAs or miRs) for EOC. Firstly, microarray analysis of miRNA expression levels was performed on 32 samples of female individuals: Eight plasma samples from patients with pathologically confirmed EOC (mean age, 45 (30-54) years), eight plasma samples from matched healthy individuals (HIs) (mean age, 44 (30-65) years), eight EOC tissue samples (mean age, 45 (30-54) years) and eight benign ovarian (mean age, 35 (17-70) years) neoplastic tissue samples A total of 31 significantly dysregulated miRNAs in serum and three miRNAs in tissue were identified by microarray. The results were validated using reverse transcription-quantitative PCR on samples from 10 patients with pathologically confirmed EOC (mean age, 47(30-54) years), 10 matched His (mean age, 40(26-65) years], 10 EOC tissue samples (mean age, 47(30-54) years) and 10 benign ovarian neoplastic tissue samples (mean age, 40(17-70) years). The 'Kyoto Encyclopedia of Genes and Genomes' (KEGG) database was used for target gene and pathway analysis. A total of three miRNAs from EOC serum (hsa-miR-1909-5p, hsa-miR-885-5p and hsa-let-7d-3p) and one microRNA from tissue samples (hsa-miR-200c-3p) were validated as significant to distinguish patients with EOC from HIs. KEGG pathway enrichment analysis showed seven significant pathways, which included 'prion diseases', 'proteoglycans in cancer', 'oxytocin signaling pathway', 'hippo signaling pathway', 'adrenergic signaling in cardiomyocytes', 'oocyte meiosis' and 'thyroid hormone signaling pathway', in which the validated miRNAs served a role. This supports the hypothesis that four validated miRNAs, have the potential to be a biomarker of EOC diagnosis and target for treatment.
上皮性卵巢癌（EOC）是死亡率最高的卵巢癌类型。由于该疾病无症状且可用的诊断测试较少，它大多在晚期才被诊断出来。因此，本研究旨在发现用于EOC的预测性和/或早期诊断性新型循环微小RNA（miRNA或miRs）。首先，对32名女性个体的样本进行了miRNA表达水平的微阵列分析：8份来自病理确诊EOC患者的血浆样本（平均年龄45（30 - 54）岁）、8份来自匹配健康个体（HI）的血浆样本（平均年龄44（30 - 65）岁）、8份EOC组织样本（平均年龄45（30 - 54）岁）和8份良性卵巢（平均年龄35（17 - 70）岁）肿瘤组织样本。通过微阵列鉴定出血清中共有31种显著失调的miRNA和组织中的3种miRNA。使用逆转录定量PCR对10名病理确诊EOC患者（平均年龄47（30 - 54）岁）、10名匹配的HI（平均年龄40（26 - 65）岁）、10份EOC组织样本（平均年龄47（30 - 54）岁）和10份良性卵巢肿瘤组织样本（平均年龄40（17 - 70）岁）的样本进行了结果验证。使用“京都基因与基因组百科全书”（KEGG）数据库进行靶基因和通路分析。来自EOC血清的3种miRNA（hsa - miR - 1909 - 5p、hsa - miR - 885 - 5p和hsa - let - 7d - 3p）和来自组织样本的1种miRNA（hsa - miR - 200c - 3p）被验证对于区分EOC患者和HI具有显著性。KEGG通路富集分析显示了7条显著通路，包括“朊病毒疾病”、“癌症中的蛋白聚糖”、“催产素信号通路”、“河马信号通路”、“心肌细胞中的肾上腺素能信号通路”、“卵母细胞减数分裂”和“甲状腺激素信号通路”，其中经过验证的miRNA在这些通路中发挥作用。这支持了以下假设，即4种经过验证的miRNA有潜力成为EOC诊断的生物标志物和治疗靶点。
