Department of Operative Gynecology, Endoscopy and Gynecologic Oncology, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
Department of Molecular Bases of Medicine, Medical University of Lodz, Lodz, Poland.
Acta Obstet Gynecol Scand. 2020 Aug;99(8):1085-1091. doi: 10.1111/aogs.13833. Epub 2020 Mar 13.
MicroRNAs (miRNAs) take part in tumorigenesis and show aberrant expression levels in cancerous tissues. We aimed to perform miRNA profiling of endometrioid endometrial cancer (EEC) metastatic loci derived from lymph nodes. Identification of aberrant miRNAs in positive lymph nodes could contribute to establishing new diagnostic markers and therapeutic targets.
During the screening phase of the study, we performed profiling of 754 human miRNAs in endometrioid endometrial cancer tissues, microdissected metastatic loci from lymph nodes and healthy lymph nodes (Taqman Array). Selection of candidate miRNAs and subsequent validation using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 50 tissue samples were performed.
After the screening phase of the study, five miRNAs were selected (hsa-miR-18b, hsa-miR-148a-5p, hsa-miR-204, hsa-miR-424, hsa-miR-129-1-3p). Validation revealed that miRNA-204 and miRNA-424 were highly downregulated in metastatic tissues compared with endometrial cancer samples (hsa-miR-204-P = .0008; hsa-miR-424-P = .0001). Receiver operating characteristic curves, which were constructed to compare endometrioid endometrial cancer and positive endometrioid endometrial cancer lymph nodes yielded the following area under the curves (AUCs): hsa-miR-204-.802 (96% confidence interval CI 0.676-0.927), hsa-miR-424-.84 (95% CI 0.711-0.969).
Compared with primary endometrioid endometrial cancer tissue, metastatic loci derived from positive lymph nodes are characterized by profound downregulation of miRNA-204 and miRNA-424.
微小 RNA(miRNA)参与肿瘤发生,在癌组织中表现出异常的表达水平。我们旨在对来源于淋巴结的子宫内膜样腺癌(EEC)转移灶进行 miRNA 谱分析。在阳性淋巴结中鉴定异常 miRNA 有助于建立新的诊断标志物和治疗靶点。
在研究的筛选阶段,我们对子宫内膜样腺癌组织、淋巴结转移灶和健康淋巴结(Taqman 微阵列)中的 754 个人类 miRNA 进行了谱分析。选择候选 miRNA,并在 50 个组织样本中使用定量逆转录聚合酶链反应(qRT-PCR)进行后续验证。
在研究的筛选阶段后,选择了 5 个 miRNA(hsa-miR-18b、hsa-miR-148a-5p、hsa-miR-204、hsa-miR-424、hsa-miR-129-1-3p)。验证结果显示,miRNA-204 和 miRNA-424 在转移组织中的表达明显低于子宫内膜样腺癌样本(hsa-miR-204-P=.0008;hsa-miR-424-P=.0001)。为了比较子宫内膜样腺癌和阳性子宫内膜样腺癌淋巴结,构建了受试者工作特征曲线,得到以下曲线下面积(AUC):hsa-miR-204-.802(96%置信区间 0.676-0.927),hsa-miR-424-.84(95%置信区间 0.711-0.969)。
与原发性子宫内膜样腺癌组织相比,来源于阳性淋巴结的转移灶表现出 miRNA-204 和 miRNA-424 的明显下调。