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KCNN3 低表达可能影响卵巢癌的耐药性。

Low expression of KCNN3 may affect drug resistance in ovarian cancer.

机构信息

Key Laboratory of Longevity and Ageing‑Related Disease of Chinese Ministry of Education, Centre for Translational Medicine and School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

Department of Gynecologic Oncology, The Affiliated Tumor Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

出版信息

Mol Med Rep. 2018 Aug;18(2):1377-1386. doi: 10.3892/mmr.2018.9107. Epub 2018 May 31.

Abstract

Drug resistance is a principal contributor to the poor prognosis of ovarian cancer (OC). Therefore, identifying factors that affect drug resistance in OC is critical. In the present study, 51 OC specimens from lab collections were immunohistochemically tested, public data for 489 samples from The Cancer Genome Atlas cohort and 1,656 samples from the Kaplan‑Meier Plotter were downloaded, and data were retrieved from Oncomine. It was identified that the mRNA and protein expression of the potassium calcium‑activated channel subfamily N member 3 (KCNN3) was markedly lower in OC tissues compared with normal tissues, and in drug‑resistant OC tissues compared with sensitive OC tissues. Low KCNN3 expression consistently predicted shorter disease‑free and overall survival (OS). Specifically, low KCNN3 expression predicted shorter OS in 395 patients with low expression levels of mucin‑16. There was additional evidence that KCNN3 expression is mediated by microRNA‑892b. Furthermore, text mining and analyses of protein and gene interactions indicated that KCNN3 affects drug resistance. To the best of the authors' knowledge, this is the first report to associate KCNN3 with poor prognosis and drug resistance in OC. The present findings indicated that KCNN3 is a potential prognostic marker and therapeutic target for OC.

摘要

耐药性是卵巢癌(OC)预后不良的主要原因。因此,确定影响 OC 耐药性的因素至关重要。在本研究中,对实验室收集的 51 份 OC 标本进行了免疫组织化学检测,下载了来自癌症基因组图谱队列的 489 份样本和 Kaplan-Meier Plotter 的 1656 份样本的公共数据,并从 Oncomine 检索了数据。研究发现,钾钙激活通道亚家族 N 成员 3(KCNN3)的 mRNA 和蛋白表达在 OC 组织中明显低于正常组织,在耐药性 OC 组织中明显低于敏感性 OC 组织。低 KCNN3 表达一致预示着无病生存期和总生存期(OS)较短。具体而言,在低表达黏蛋白 16 的 395 名患者中,低 KCNN3 表达预示着 OS 较短。还有证据表明,KCNN3 的表达受 microRNA-892b 的调节。此外,文本挖掘和蛋白质-基因相互作用分析表明,KCNN3 影响药物耐药性。据作者所知,这是首次将 KCNN3 与 OC 的不良预后和耐药性相关联。本研究结果表明,KCNN3 是 OC 的一个潜在的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7033/6072180/536058d62a6c/MMR-18-02-1377-g00.jpg

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