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血清miR-483-5p作为检测肝细胞癌的潜在生物标志物。

Serum miR-483-5p as a potential biomarker to detect hepatocellular carcinoma.

作者信息

Zhang Zhoujing, Ge Shengxiang, Wang Xiaomin, Yuan Quan, Yan Qiang, Ye Huiming, Che Yaojian, Lin Yanyan, Zhang Jun, Liu Pingguo

机构信息

Clinical Laboratory Center, Zhongshan Hospital of Xiamen University, 209 Hubin South Road, Xiamen, 361004, Fujian, China.

National Institute of Diagnostic and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, Fujian, China.

出版信息

Hepatol Int. 2013 Mar;7(1):199-207. doi: 10.1007/s12072-012-9341-z. Epub 2012 Feb 7.

Abstract

BACKGROUND AND GOALS

There are no highly sensitive and specific minimally invasive biomarkers for hepatocellular carcinoma (HCC) to date. The objective of this study was to identify serum microRNAs (miRNAs) as potential HCC biomarkers.

METHODS

Using miRCURY LNA™ microRNA arrays, the levels of circulating miRNAs in the serum of patients with HCC were compared and controls were matched. Then 253 subjects (112 HCC, 85 chronic hepatitis B [CHB], and 56 healthy controls) were recruited and 12 serum miRNAs were compared by quantitative real-time polymerase chain reaction (qRT-PCR). It was followed by the comparison of serum miRNA concentrations before and after the surgical resection in HCC group.

RESULTS

Median levels of miR-483-5p and miR-500a were higher in HCC patients than in patients with CHB and in healthy controls (p < 0.0001), but there were no differences between CHB patients and healthy controls (p > 0.05) and miR-483-5p levels were significantly reduced in serum samples obtained 30 days after surgical resection (p < 0.0001). The area under receiver operating characteristic curves of miR-483-5p and miR-500a was 74% (cutoff [Ct] value = 2.824, sensitivity = 74%, and specificity = 66%) and 66% (Ct value = 1.830, sensitivity = 74%, and specificity = 51%) for the prediction of HCC, respectively. In detecting HCC, combining α-fetoprotein (AFP) and serum miR-483-5p (sensitivity = 81% and specificity = 83%) was better than AFP alone (sensitivity = 78%, specificity = 70%).

CONCLUSION

Our observations suggest that serum miR-483-5p and miR-500a might serve as novel, noninvasive biomarkers for HCC. Serum miR-483-5p might complement AFP in detecting HCC.

摘要

背景与目标

目前尚无用于肝细胞癌(HCC)的高敏感性和特异性的微创生物标志物。本研究的目的是鉴定血清微小RNA(miRNA)作为潜在的HCC生物标志物。

方法

使用miRCURY LNA™微小RNA芯片,比较HCC患者血清中循环miRNA的水平,并匹配对照。然后招募了253名受试者(112例HCC、85例慢性乙型肝炎[CHB]和56例健康对照),并通过定量实时聚合酶链反应(qRT-PCR)比较了12种血清miRNA。随后比较了HCC组手术切除前后的血清miRNA浓度。

结果

HCC患者中miR-483-5p和miR-500a的中位水平高于CHB患者和健康对照(p < 0.0001),但CHB患者与健康对照之间无差异(p > 0.05),且手术切除30天后获得的血清样本中miR-483-5p水平显著降低(p < 0.0001)。miR-483-5p和miR-500a预测HCC的受试者操作特征曲线下面积分别为74%(临界值[Ct] = 2.824,敏感性 = 74%,特异性 = 66%)和66%(Ct值 = 1.830,敏感性 = 74%,特异性 = 51%)。在检测HCC时,联合甲胎蛋白(AFP)和血清miR-483-5p(敏感性 = 81%,特异性 = 83%)比单独使用AFP(敏感性 = 78%,特异性 = 70%)更好。

结论

我们的观察结果表明,血清miR-483-5p和miR-500a可能作为HCC新的非侵入性生物标志物。血清miR-483-5p在检测HCC时可能补充AFP的作用。

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