Huang Qing, Wang Changjiang, Hou Ziming, Wang Gang, Lv Jianghua, Wang Hao, Yang Jun, Zhang Zhe, Zhang Hongbing
Cancer Biomark. 2017;19(2):137-144. doi: 10.3233/CBM-160146.
MicroRNA (miR)-376 family play crucial roles in cancer formation and progression.
To investigate expression patterns of circulating miR-376 members in glioma patients, and to explore their diagnostic and prognostic values.
Expression of miR-376 members in serum samples from 100 glioma patients and 50 healthy controls were detected by quantitative real-time PCR.
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.
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.
微小RNA(miR)-376家族在癌症的形成和进展中起关键作用。
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。
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。
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。
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。