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血清微小RNA-376家族作为人类胶质瘤的诊断和预后标志物

Serum microRNA-376 family as diagnostic and prognostic markers in human gliomas.

作者信息

Huang Qing, Wang Changjiang, Hou Ziming, Wang Gang, Lv Jianghua, Wang Hao, Yang Jun, Zhang Zhe, Zhang Hongbing

出版信息

Cancer Biomark. 2017;19(2):137-144. doi: 10.3233/CBM-160146.

Abstract

BACKGROUND

MicroRNA (miR)-376 family play crucial roles in cancer formation and progression.

OBJECTIVE

To investigate expression patterns of circulating miR-376 members in glioma patients, and to explore their diagnostic and prognostic values.

METHODS

Expression of miR-376 members in serum samples from 100 glioma patients and 50 healthy controls were detected by quantitative real-time PCR.

RESULTS

Serum miR-376a, miR-376b and miR-376c in glioma patients were significantly lower than those in healthy controls (all P< 0.05). Their expression could efficiently distinguish the glioma patients from healthy controls according to the receiver operating characteristic (ROC) analysis [for miR-376a, the area under ROC curve (AUC) = 0.872, the optimal cut-off value = 1.95, the sensitivity = 81.0% and the specificity = 82.0%; for miR-376b, AUC = 0.890, the optimal cut-off value = 2.07, the sensitivity = 82.0% and the specificity = 78.0%; for miR-376c, AUC = 0.837, the optimal cut-off value = 2.12, the sensitivity = 90.0% and the specificity = 70.0%; all P<0. 001]. Decreased expression of miR-376a, miR-376b and miR-376c in patients' sera were significantly associated with advanced WHO grade (all P< 0.01) and low KPS (all P< 0.05). Kaplan-Meier and Cox regression analyses showed that low miR-376a, miR-376b and miR-376c expression, and high grade were all independent factors predicting poor outcome of glioma patients. Notably, subgroup analyses showed that serum miR-376a, miR-376b and miR-376c levels had more significant prognostic values in patients with high grade gliomas than those with low grade gliomas.

CONCLUSIONS

Aberrant expression of the miR-376 family may be involved into tumorigenesis and tumor progression of human gliomas. Circulating miR-376a, miR-376b and miR-376c may be promising non-invasive biomarkers for diagnosis and prognosis in glioma patients.

摘要

背景

微小RNA(miR)-376家族在癌症的形成和进展中起关键作用。

目的

研究胶质瘤患者循环miR-376成员的表达模式,并探讨其诊断和预后价值。

方法

采用定量实时PCR检测100例胶质瘤患者和50例健康对照血清样本中miR-376成员的表达。

结果

胶质瘤患者血清miR-376a、miR-376b和miR-376c水平显著低于健康对照(均P<0.05)。根据受试者工作特征(ROC)分析,它们的表达能有效区分胶质瘤患者和健康对照[miR-376a,ROC曲线下面积(AUC)=0.872,最佳截断值=1.95,灵敏度=81.0%,特异度=82.0%;miR-376b,AUC=0.890,最佳截断值=2.07,灵敏度=82.0%,特异度=78.0%;miR-376c,AUC=0.837,最佳截断值=2.12,灵敏度=90.0%,特异度=70.0%;均P<0.001]。患者血清中miR-376a、miR-376b和miR-376c表达降低与世界卫生组织(WHO)高级别显著相关(均P<0.01),与低KPS显著相关(均P<0.05)。Kaplan-Meier和Cox回归分析表明,miR-376a、miR-376b和miR-376c低表达以及高级别都是预测胶质瘤患者预后不良的独立因素。值得注意的是,亚组分析表明,血清miR-376a、miR-376b和miR-376c水平在高级别胶质瘤患者中的预后价值比低级别胶质瘤患者更显著。

结论

miR-376家族的异常表达可能参与了人类胶质瘤的发生和肿瘤进展。循环miR-376a、miR-376b和miR-376c可能是有前景的用于胶质瘤患者诊断和预后的非侵入性生物标志物。

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