尿液中的微小RNA-30a-5p是卵巢浆液性腺癌的一种潜在生物标志物。
Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma.
作者信息
Zhou Jun, Gong Guanghui, Tan Hong, Dai Furong, Zhu Xin, Chen Yile, Wang Junpu, Liu Ying, Chen Puxiang, Wu Xiaoying, Wen Jifang
机构信息
Department of Pathology, School of Basic Medical Science, Central South University, Changsha, Hunan 410013, P.R. China.
Department of Gynecology and Obstetrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
出版信息
Oncol Rep. 2015 Jun;33(6):2915-23. doi: 10.3892/or.2015.3937. Epub 2015 Apr 28.
MicroRNAs (miRNAs) can serve as biomarkers in human cancer. To determine the clinical value of urinary miRNAs for ovarian serous adenocarcinoma, we collected urine samples from 39 ovarian serous adenocarcinoma patients, 26 patients with benign gynecological disease and 30 healthy controls. The miRNA microarray data showed that only miR-30a-5p was upregulated and 37 miRNAs were downregulated in the urine samples of ovarian serous adenocarcinoma patients, when compared to healthy controls, which was confirmed after conducting quantitative PCR. The upregulation of urinary miR-30a-5p was closely associated with early stage of ovarian serous adenocarcinoma as well as lymphatic metastasis. Receiver operator characteristic (ROC) analysis demonstrated the potential use of urinary miR-30a-5p as a diagnostic marker for ovarian serous adenocarcinoma. Furthermore, a lower urine level of miR-30a-5p was found in 20 gastric cancer and 20 colon carcinoma patients when compared to ovarian serous adenocarcinoma, suggesting that the upregulation of urinary miR-30a-5p may be specific for ovarian serous adenocarcinoma. miR-30a-5p was also upregulated in ovarian serous adenocarcinoma tissues and cell lines, while urinary miR-30a-5p from ovarian cancer patients was notably reduced following the surgical removal of ovarian serous adenocarcinoma, suggesting that urinary miR-30a-5p was derived from the ovarian serous adenocarcinoma tissue. Notably, miR-30a-5p was concentrated with exosomes from the ovarian cancer cell supernatant or urine from ovarian serous adenocarcinoma patients, supporting a pathway for excretion into the urine. The results also showed that the knockdown of miR-30a-5p significantly inhibited the proliferation and migration of ovarian cancer cells. In summary, to the best of our knowledge, the present study provided the first evidence of increased miR-30a-5p in the urine of ovarian serous adeno-carcinoma patients, while the inhibition of miR-30a-5p suppressed the malignant phenotypes of ovarian cancer in vitro. Therefore, miR-30a-5p serves as a promising diagnostic and therapeutic target for ovarian serous adenocarcinoma.
微小RNA(miRNA)可作为人类癌症的生物标志物。为了确定尿miRNA对卵巢浆液性腺癌的临床价值,我们收集了39例卵巢浆液性腺癌患者、26例良性妇科疾病患者和30例健康对照者的尿液样本。miRNA微阵列数据显示,与健康对照相比,卵巢浆液性腺癌患者尿液样本中仅miR-30a-5p上调,37种miRNA下调,定量PCR后得到证实。尿miR-30a-5p的上调与卵巢浆液性腺癌的早期阶段以及淋巴转移密切相关。受试者工作特征(ROC)分析表明尿miR-30a-5p有可能作为卵巢浆液性腺癌的诊断标志物。此外,与卵巢浆液性腺癌相比,20例胃癌和20例结肠癌患者的尿miR-30a-5p水平较低,提示尿miR-30a-5p的上调可能对卵巢浆液性腺癌具有特异性。miR-30a-5p在卵巢浆液性腺癌组织和细胞系中也上调,而卵巢浆液性腺癌手术切除后,卵巢癌患者的尿miR-30a-5p显著降低,提示尿miR-30a-5p来源于卵巢浆液性腺癌组织。值得注意的是,miR-30a-5p与卵巢癌细胞上清液中的外泌体或卵巢浆液性腺癌患者的尿液中的外泌体共浓缩,支持其排泄到尿液中的途径。结果还表明,敲低miR-30a-5p可显著抑制卵巢癌细胞的增殖和迁移。总之,据我们所知,本研究首次证明卵巢浆液性腺癌患者尿液中miR-30a-5p增加,而抑制miR-30a-5p可在体外抑制卵巢癌的恶性表型。因此,miR-30a-5p有望成为卵巢浆液性腺癌的诊断和治疗靶点。