Günel Tuba, Gumusoglu Ece, Dogan Berkcan, Ertem Fatma Betül, Hosseini Mohammad Kazem, Cevik Nazife, Senol Taylan, Topuz Samet, Aydinli Kilic
Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, 34134 Sehzadebasi Ave, 34134, Istanbul, Turkey.
Computer Engineering Department, Engineering, Architecture Faculty, Istanbul Arel University, 34537, Istanbul, Turkey.
Arch Gynecol Obstet. 2018 Dec;298(6):1173-1180. doi: 10.1007/s00404-018-4913-3. Epub 2018 Sep 27.
Ovarian cancer (OC) is first gynaecologic cancer that causes women death and epithelial ovarian cancer (EOC) is the most lethal ovarian cancer type. While treatment is commonly successful, some cases (10-20%) show resistance to chemotherapy which is followed by recurrence. MicroRNA (miRNA) based diagnosis methods are slightly important for recurrent ovarian cancer diagnosis. We aimed to detect novel circulating miRNAs to be used as an early diagnosis and prediction tools for recurrent EOC.
In this study, recurrent EOC serum samples and healthy control serum samples were compared for miRNA expression analysis by microarray. Microarray results were analyzed by bioinformatics tools and differentially expressed hsa-miR-1273g-3p was obtained. After microarray analysis, differentially expressed hsa-miR-1273g-3p was validated by Real-Time PCR (RT-qPCR). The relation between target genes of hsa-miR-1273g-3p and ovarian cancer were examined by Pathway Studio (v.11.4.0.8).
The expression of hsa-miR-1273g-3p was found to be significantly down-regulated by t test Bonferroni FWER corrected p < 0.05 and fold change > 2, in recurrence EOC compare with healthy controls groups. The RT-qPCR results confirmed that relative expressions of the serum hsa-miR-1273g-3p were significantly down-regulated in patients with recurrent EOC (p = 0.0275). Serum hsa-miR-1273g-3p levels could discriminate patients with recurrent EOC from healthy controls, with a power area under the curve (AUC) of 0.7.
This study suggested that hsa-miR-1273g-3p plays a significant role in regulation of related genes, which are TNF-alfa, COL1A1, MMP-2, MMP-9, with recurrent EOC outcome. hsa-miR-1273g-3p may be used as a prognostic marker for recurrent EOC after chemotherapy.
卵巢癌（OC）是导致女性死亡的首要妇科癌症，上皮性卵巢癌（EOC）是最致命的卵巢癌类型。虽然治疗通常很成功，但一些病例（10 - 20%）对化疗表现出耐药性，随后会复发。基于微小RNA（miRNA）的诊断方法对复发性卵巢癌的诊断具有一定重要性。我们旨在检测新型循环miRNA，以用作复发性EOC的早期诊断和预测工具。
在本研究中，通过微阵列比较复发性EOC血清样本和健康对照血清样本的miRNA表达分析。微阵列结果通过生物信息学工具进行分析，获得差异表达的hsa-miR-1273g-3p。微阵列分析后，通过实时定量聚合酶链反应（RT-qPCR）验证差异表达的hsa-miR-1273g-3p。通过Pathway Studio（v.11.4.0.8）检查hsa-miR-1273g-3p的靶基因与卵巢癌之间的关系。
通过t检验Bonferroni校正错误发现率（FWER），校正后p < 0.05且倍数变化> 2，发现与健康对照组相比，复发性EOC中hsa-miR-1273g-3p的表达显著下调。RT-qPCR结果证实，复发性EOC患者血清hsa-miR-1273g-3p的相对表达显著下调（p = 0.0275）。血清hsa-miR-1273g-3p水平能够区分复发性EOC患者与健康对照，曲线下面积（AUC）为0.7。
本研究表明，hsa-miR-1273g-3p在调节与复发性EOC结局相关的基因（如肿瘤坏死因子-α、I型胶原蛋白α1链、基质金属蛋白酶-2、基质金属蛋白酶-9）中起重要作用。hsa-miR-1273g-3p可作为化疗后复发性EOC的预后标志物。
