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循环促血管生成 miRNA 表达与胃癌发病风险、临床病理特征和生存状况的相关性。

The correlation of circulating pro-angiogenic miRNAs' expressions with disease risk, clinicopathological features, and survival profiles in gastric cancer.

机构信息

Department of General Surgery, Guangdong General Hospital Zhuhai Hospital (Zhuhai Golden Bay Center Hospital), Zhuhai, China.

Deparment of General Surgery, No. 211 Hospital of PLA, Harbin, China.

出版信息

Cancer Med. 2018 Aug;7(8):3773-3791. doi: 10.1002/cam4.1618. Epub 2018 Jul 12.

Abstract

This study aimed to explore the correlation of circulating pro-angiogenic miRNAs' expressions with risk, clinicopathological features, and survival profiles in gastric cancer (GC). Three hundred and thirty-three GC patients underwent radical resection and 117 health controls (HCs) were recruited for this study. Plasma samples were obtained from GC patients before the operation and from HCs after enrollment. Fourteen pro-angiogenic miRNAs were asseassed by quantitative polymerase chain reaction (qPCR). Disease-free survival (DFS) and overall survival (OS) of GC patients were calculated and the median follow-up duration was 36.0 months. Seven out of 14 pro-angiogenic miRNAs including let-7f, miR-17-5p, miR-18a, miR-19b-1, miR-20a, miR-210, and miR-296 were observed to be elevated in GC patients compared with HCs. MiR-18a, miR-20a, and miR-210 disclosed good predictive values of GC risk. Six pro-angiogenic miRNAs including miR-17-5p, miR-92a, miR-210, miR-20a, miR-18a, and miR-296 expressions were positively while 1 pro-angiogenic miRNA (miR-130a) was negatively correlated with tumor malignancy degree in GC patients. K-M curve disclosed that 5 pro-angiogenic miRNAs including miR-17-5p, miR-18a, miR-20a, miR-92a, and miR-210 correlated with worse DFS, while 4 pro-angiogenic miRNAs including miR-17-5p, miR-18a, miR-20a, and miR-210 associated with shorter OS. Further multivariate Cox's analysis revealed that miR-17-5p, miR-18a, miR-20a, and miR-210 were independent predictive factors for unfavorable DFS and OS. In conclusion, circulating pro-angiogenic miRNAs could serve as novel noninvasive biomarkers for disease risk and malignancy degree, and miR-17-5p, miR-18a, miR-20a, and miR-210 are independent factors predicting poor prognosis in GC patients.

摘要

本研究旨在探讨循环促血管生成 miRNA 的表达与胃癌(GC)风险、临床病理特征和生存状况的相关性。对 333 例接受根治性切除术的 GC 患者和 117 例健康对照者(HCs)进行了这项研究。在手术前从 GC 患者和在入组后从 HCs 获得血浆样本。通过定量聚合酶链反应(qPCR)检测了 14 种促血管生成 miRNA。计算了 GC 患者的无病生存(DFS)和总生存(OS),中位随访时间为 36.0 个月。与 HCs 相比,GC 患者中发现有 7 种促血管生成 miRNA(let-7f、miR-17-5p、miR-18a、miR-19b-1、miR-20a、miR-210 和 miR-296)升高。miR-18a、miR-20a 和 miR-210 显示出对 GC 风险的良好预测值。在 GC 患者中,6 种促血管生成 miRNA(miR-17-5p、miR-92a、miR-210、miR-20a、miR-18a 和 miR-296)表达呈正相关,而 1 种促血管生成 miRNA(miR-130a)与肿瘤恶性程度呈负相关。K-M 曲线显示,5 种促血管生成 miRNA(miR-17-5p、miR-18a、miR-20a、miR-92a 和 miR-210)与较差的 DFS 相关,而 4 种促血管生成 miRNA(miR-17-5p、miR-18a、miR-20a 和 miR-210)与较短的 OS 相关。进一步的多变量 Cox 分析表明,miR-17-5p、miR-18a、miR-20a 和 miR-210 是不利 DFS 和 OS 的独立预测因素。总之,循环促血管生成 miRNA 可作为疾病风险和恶性程度的新型无创生物标志物,miR-17-5p、miR-18a、miR-20a 和 miR-210 是 GC 患者预后不良的独立因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/6089172/75f07dbb8f73/CAM4-7-3773-g001.jpg

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