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血清 microRNA 表达谱分析鉴定出与 HCV 相关的肝细胞癌的血清生物标志物。

Serum microRNA expression profiling identifies serum biomarkers for HCV-related hepatocellular carcinoma.

机构信息

Department of Hepatobiliary Surgery, Hospital Affiliated to Chengde Medical University, Chengde, Hebei, China.

Department of Hepatobiliary Surgery, You'an Hospital Affiliated to Capital Medical University, Beijing, China.

出版信息

Cancer Biomark. 2019;26(4):501-512. doi: 10.3233/CBM-181970.

Abstract

BACKGROUND

The identification of high-sensitivity biomarkers for detection of hepatocellular carcinoma (HCC) from high-risk individuals is essential.

OBJECTIVE

The present study was undertaken to identify and validate serum microRNAs (miRNAs) as potential biomarkers for hepatitis C virus (HCV)-related HCC.

METHODS

Illumina sequencing was employed to screen the expression profiles of miRNAs in serum samples of HCV-related HCC patients and liver cirrhosis (LC) patients. RT-qPCR was used to confirm the altered miRNAs between the two groups. Moreover, candidate miRNAs were examined in serum samples of 40 HCC patients, 54 LC patients, 55 patients with chronic HCV hepatitis and 45 healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the miRNAs for the detection of HCC.

RESULTS

Four miRNAs (miR-122-5p, miR-331-3p, miR-494-3p, miR-224-5p) were significantly increased and two miRNAs (miR-185-5p, miR-23b-3p) were significantly decreased in HCC patients compared to LC patients. ROC curve analysis demonstrated that the six miRNAs could be used as potential biomarkers for HCC detection. Combination of the six miRNAs could efficiently detect HCC in LC patients with the area under the ROC curve (AUC) of 0.995 and combination of the six miRNAs also provided high diagnostic accuracy (AUC = 0.961) for detection of HCC in non-HCC subjects.

CONCLUSIONS

The six serum miRNAs can be utilized as a surrogate and non-invasive biomarker for HCV-related HCC diagnosis.

摘要

背景

从高危人群中识别出用于检测肝细胞癌 (HCC) 的高灵敏度生物标志物至关重要。

目的

本研究旨在鉴定和验证血清 microRNAs (miRNAs) 作为丙型肝炎病毒 (HCV) 相关 HCC 的潜在生物标志物。

方法

采用 Illumina 测序筛选 HCV 相关 HCC 患者和肝硬化 (LC) 患者血清样本中的 miRNA 表达谱。采用 RT-qPCR 验证两组之间改变的 miRNA。此外,在 40 例 HCC 患者、54 例 LC 患者、55 例慢性 HCV 肝炎患者和 45 例健康对照者的血清样本中检测候选 miRNA。采用受试者工作特征 (ROC) 曲线分析评估 miRNA 用于 HCC 检测的诊断性能。

结果

与 LC 患者相比,HCC 患者中有 4 个 miRNA(miR-122-5p、miR-331-3p、miR-494-3p、miR-224-5p)显著上调,2 个 miRNA(miR-185-5p、miR-23b-3p)显著下调。ROC 曲线分析表明,这 6 个 miRNA 可作为 HCC 检测的潜在生物标志物。这 6 个 miRNA 的组合可有效检测 LC 患者中的 HCC,ROC 曲线下面积 (AUC) 为 0.995,并且 6 个 miRNA 的组合也为非 HCC 患者 HCC 的检测提供了较高的诊断准确性 (AUC=0.961)。

结论

这 6 种血清 miRNAs 可作为 HCV 相关 HCC 诊断的替代和非侵入性生物标志物。

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