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检测外泌体酪氨酸受体激酶 B 作为卵巢癌的潜在生物标志物。

Detection of exosomal tyrosine receptor kinase B as a potential biomarker in ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Department of Obstetrics and Gynecology, Dalian Medical University Affiliated Dalian Obstetrics and Gynecology Hospital, Dalian, China.

出版信息

J Cell Biochem. 2019 Apr;120(4):6361-6369. doi: 10.1002/jcb.27923. Epub 2018 Oct 10.

DOI:10.1002/jcb.27923
PMID:30304550
Abstract

Ovarian cancer (OC) is a lethal disease diagnosed at advanced stages due to the lack of specific biomarkers. Tyrosine receptor kinase B (TrkB), which has recently been found to be related to OC progression, represents a promising potential biomarker for OC diagnosis and prognosis. The discovery of circulating exosomes as biomarkers for various diseases led us to explore exosomal TrkB in OC. Our previous study proved that the expression of TrkB was elevated in OC tissues. In this study, we focused on the detection of exosomal TrkB in OC. Exosomes were first gathered from three different OC cell lines' conditioned medium, serum samples of patients with OC as well as xenograft mice serum by serial centrifugation method. Then, we identified exosomes by transmission electron microscopy, NanoSight analysis, and expression of typical exosomal protein markers. The existence of TrkB in exosomes was measured by Western blot analysis, and the expression was detected by enzyme-linked immunosorbent assay. In this study, we demonstrated that exosomes could derive from OC cell lines, serum from OC xenograft nude mice, and clinical patients. Our study shows that serum exosomal TrkB may be considered a minimally invasive biomarker for OC.

摘要

卵巢癌(OC)是一种致命疾病,由于缺乏特异性生物标志物,通常在晚期才被诊断出来。酪氨酸受体激酶 B(TrkB)最近被发现与 OC 的进展有关,它是 OC 诊断和预后的有前途的潜在生物标志物。循环外泌体作为各种疾病生物标志物的发现促使我们探索 OC 中外泌体 TrkB。我们之前的研究证明了 TrkB 在 OC 组织中的表达上调。在这项研究中,我们专注于检测 OC 中外泌体 TrkB。首先通过连续离心法从三种不同的 OC 细胞系的条件培养基、OC 患者的血清样本以及异种移植裸鼠的血清中收集外泌体。然后,通过透射电子显微镜、纳米粒子跟踪分析和典型外泌体蛋白标志物的表达来鉴定外泌体。通过 Western blot 分析测量外泌体中 TrkB 的存在,并通过酶联免疫吸附测定检测表达。在这项研究中,我们证明了外泌体可以来源于 OC 细胞系、OC 异种移植裸鼠的血清和临床患者的血清。我们的研究表明,血清外泌体 TrkB 可以被认为是 OC 的一种微创生物标志物。

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