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血浆miR-940可能作为胃癌的一种新型生物标志物。

Plasma miR-940 may serve as a novel biomarker for gastric cancer.

作者信息

Liu Xin, Kwong Ava, Sihoe Alan, Chu Kent-Man

机构信息

Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.

出版信息

Tumour Biol. 2016 Mar;37(3):3589-97. doi: 10.1007/s13277-015-4019-5. Epub 2015 Oct 11.

Abstract

It was reported that circulating microRNAs could be applied as non-invasive biomarkers for cancer monitoring. The purpose of this study was to identify plasma miRNA that may serve as a novel biomarker for gastric cancer and to evaluate its clinical application. MicroRNA profiles were generated from plasma samples of 5 patients with gastric cancer (GC) versus 5 healthy controls (HC). MicroRNA-940 (miR-940) was one of the most downregulated miRNAs with fold change of 0.164. It was revealed that the expression of miR-940 was downregulated in both the initial set (N = 30, P < 0.0001) and the validation set (N = 80, P < 0.0001) of plasma samples of patients with gastric cancer. The sensitivity was obviously higher than the current biomarkers CEA and CA19-9 (81.25 % vs. 22.54 % and 15.71 %). MiR-940 was also significantly downregulated in gastric cancer tissue samples (N = 34, P = 0.0015), as well as in cancer cell lines (N = 7). Importantly, miR-940 was significantly highly expressed in stomach tissue samples than in other types of tissue samples including the liver, breast, thyroid, and lung. Moreover, there was a trend of lower expression of miR-940 from early to advanced stage of gastric cancer. Target prediction suggested that miR-940 regulated cell signaling including NF-κB and Wnt/β-catenin, as well as pathways of cell communication and adhesion. These pathways play critical roles in gastric cancer initiation and progression. It is the first report that miR-940 may mainly express in the stomach. Downregulation of plasma miR-940 may serve as a novel biomarker for detection of gastric cancer.

摘要

据报道,循环微小RNA可作为癌症监测的非侵入性生物标志物。本研究的目的是鉴定可能作为胃癌新型生物标志物的血浆微小RNA,并评估其临床应用价值。对5例胃癌(GC)患者和5例健康对照(HC)的血浆样本进行了微小RNA谱分析。微小RNA-940(miR-940)是下调最为显著的微小RNA之一,其倍数变化为0.164。结果显示,在胃癌患者血浆样本的初始队列(N = 30,P < 0.0001)和验证队列(N = 80,P < 0.0001)中,miR-940的表达均下调。其敏感性明显高于目前的生物标志物癌胚抗原(CEA)和糖类抗原19-9(81.25% 对22.54% 和15.71%)。在胃癌组织样本(N = 34,P = 0.0015)以及癌细胞系(N = 7)中,miR-940也显著下调。重要的是,与包括肝脏、乳腺、甲状腺和肺在内的其他类型组织样本相比,miR-940在胃组织样本中显著高表达。此外,从胃癌早期到晚期,miR-940的表达有降低趋势。靶标预测表明,miR-940调控包括核因子κB(NF-κB)和Wnt/β-连环蛋白在内的细胞信号通路,以及细胞通讯和黏附途径。这些途径在胃癌的发生和发展中起关键作用。这是首次报道miR-940可能主要在胃中表达。血浆miR-940的下调可能作为检测胃癌的新型生物标志物。

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