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循环 DSCAM-AS1 在 ER 阳性乳腺癌患者中的临床意义及其竞争性内源 RNA 网络的构建。

The clinical significance of circulating DSCAM-AS1 in patients with ER-positive breast cancer and construction of its competitive endogenous RNA network.

机构信息

Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Medical Biology Research Center, Medical School, Kermanshah University of Medical Sciences, Daneshgah Avenue, P.O. Box 67148‑69914, Kermanshah, Iran.

出版信息

Mol Biol Rep. 2020 Oct;47(10):7685-7697. doi: 10.1007/s11033-020-05841-5. Epub 2020 Oct 11.

Abstract

Long Non-Coding RNAs (lncRNAs), with diagnostic and therapeutic applications in malignancies, are newly described tumour-related molecules. Here, we reported the importance of circulating DSCAM-AS1 as the biomarker to detect Estrogen Receptor (ER)-positive breast cancer (BC) cases. Moreover, the expression of a BC-associated lncRNAs, namely DSCAM-AS1, was measured in tumoural and Paired Adjacent Non-Tumoral (PANT) tissue, as well as plasma, using Real-Time Polymerase Chain Reaction (RT-PCR). Besides, the correlations between gene expression and the clinicopathological features were analyzed. The diagnostic power of circulating DSCAM-AS1 in BC was estimated using the Area Under the Curve (AUC) value. Furthermore, we studied the DSCAM-AS1 associated with the network of competitive endogenous RNA (ceRNA) in BC using the literature review and in silico analysis. We found a significant increase in the expression levels of lncRNA in the tumour (P < 0.001) and in plasma (P < 0.001) of ER-positive BC patients. The sensitivity and specificity of DSCAM-AS1 in plasma for detection of BC from healthy controls were 100 and 97%, respectively (AUC = 0.98, P < 0.001). Accordingly, we suggest an elevated level of circulating DSCAM-AS1 as a candidate biomarker of ER-positive BC patients. Moreover, perturbation of DSCAM-AS1, as a ceRNA, acts in the tumor progression and drug resistance by affecting different cell signaling.

摘要

长链非编码 RNA(lncRNAs)作为诊断和治疗恶性肿瘤的应用,是新描述的肿瘤相关分子。在这里,我们报道了循环 DSCAM-AS1 作为检测雌激素受体(ER)阳性乳腺癌(BC)病例的生物标志物的重要性。此外,使用实时聚合酶链反应(RT-PCR)测量肿瘤和配对相邻非肿瘤(PANT)组织以及血浆中与 BC 相关的 lncRNAs(即 DSCAM-AS1)的表达。此外,分析了基因表达与临床病理特征之间的相关性。使用曲线下面积(AUC)值估计循环 DSCAM-AS1 在 BC 中的诊断能力。此外,我们使用文献回顾和计算机分析研究了与 BC 中竞争性内源性 RNA(ceRNA)网络相关的 DSCAM-AS1。我们发现 ER 阳性 BC 患者肿瘤(P < 0.001)和血浆(P < 0.001)中 lncRNA 的表达水平显着增加。DSCAM-AS1 在血浆中检测 BC 对健康对照的敏感性和特异性分别为 100%和 97%(AUC = 0.98,P < 0.001)。因此,我们建议循环 DSCAM-AS1 水平升高作为 ER 阳性 BC 患者的候选生物标志物。此外,DSCAM-AS1 作为 ceRNA 的扰动通过影响不同的细胞信号转导在肿瘤进展和耐药性中起作用。

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