Zhang Meifeng, Wu Wei, Gao Ming, Fei Zhewei
Cancer Biomark. 2017 Jul 4;19(4):437-445. doi: 10.3233/CBM-170059.
To investigate the diagnostic potentials of microRNA-451(miR-451) in papillary thyroid carcinoma (PTC) diagnosis and lymph node (LN) metastasis, formalin-fixed, paraffin-embedded (FFPE) tissue specimens corresponding to PTC tumors (n= 60) and their normal counterparts (Normal tissues Adjacent to Tumor, NAT, n= 60), along with sera from PTC patients with malignant tumors (n= 70) and benign lesions (n= 70) were analyzed for the expression of miR-451 by real-time PCR.
The usefulness of miR-451 expression as a prognostic marker for diagnosis of PTC malignancies was evaluated by Receiver Operating Curve (ROC). We reported that when compared to those in NAT, the levels of miR-451 in FFPE tissues from various stages of PTC patients (n= 60) were significantly lower (Mean ± SEM; 12.62 ± 1.73 vs 38.8 ± 3.51, p< 0.0001). Receiver operating curve (ROC) analysis revealed that the area under curve (AUC) was 0.808; suggesting miR-451 expression was a reliable tissue biomarker for PTC malignancies. Further in depth analyses of these specimens revealed that miR-451 levels were significantly lower in PTC patients with lymph node (LN) metastasis than those without LN metastasis (3.96 ± 1.67 vs. 14.15 ± 1.95, p= 0.006) with calculated AUC of 0.792, supporting the notion that miR-451 expression was also a good indicator for PTC lymph node involvements. Analyses sera from the cohorts of PTC patients indicated that miR-451 levels in patients with malignant lesions (n= 70) were significantly lower (10.72 ± 1.52 vs. 19.28 ± 2.73, p= 0.010) than those with benign ones (n= 70). Parallel analyses of serum miR-451 levels in patients with LN metastasis also showed that they were significantly lower when compared to those without LN metastasis (6.79 ± 2.29 vs. 12.08 ± 1.86, p= 0.017).
ROC analyses revealed that AUC was 0.626 for malignancies and was 0.690 for lymph node involvement, respectively, suggesting that miR-451was a modest blood based biomarker for PTC malignancies and lymph node metastasis.
We concluded that miR-451 expression is a reliable FFPE tissue biomarker for PTC malignancies and it may have potentials to become a noninvasive, blood-based biomarker for PTC diagnosis and evaluation of LN status.
为研究微小RNA-451（miR-451）在甲状腺乳头状癌（PTC）诊断及淋巴结（LN）转移中的诊断潜力，采用实时定量聚合酶链反应（PCR）分析了60例PTC肿瘤及其相应正常对照组织（肿瘤旁正常组织，NAT，n = 60）的福尔马林固定石蜡包埋（FFPE）组织标本，以及70例PTC恶性肿瘤患者和70例良性病变患者的血清中miR-451的表达情况。
采用受试者工作特征曲线（ROC）评估miR-451表达作为PTC恶性肿瘤诊断预后标志物的有效性。我们发现，与NAT相比，不同分期PTC患者（n = 60）FFPE组织中miR-451水平显著降低（均值±标准误；12.62±1.73 vs 38.8±3.51，p<0.0001）。ROC分析显示曲线下面积（AUC）为0.808，提示miR-451表达是PTC恶性肿瘤可靠的组织生物标志物。对这些标本的进一步深入分析显示，有淋巴结（LN）转移的PTC患者miR-451水平显著低于无LN转移者（3.96±1.67 vs. 14.15±1.95，p = 0.006），计算得到的AUC为0.792，支持miR-451表达也是PTC淋巴结受累良好指标的观点。对PTC患者队列血清的分析表明，恶性病变患者（n = 70）的miR-451水平显著低于良性病变患者（n = 70）（10.72±1.52 vs. 19.28±（此处原文有误，应为2.73），p = 0.010）。对有LN转移患者血清miR-451水平的平行分析也显示，与无LN转移者相比，其水平显著降低（6.79±2.29 vs. 12.08±1.86，p = 0.017）。
ROC分析显示，恶性肿瘤的AUC为0.626，淋巴结受累的AUC为0.690，提示miR-451是PTC恶性肿瘤和淋巴结转移的中等水平血液生物标志物。
我们得出结论，miR-451表达是PTC恶性肿瘤可靠的FFPE组织生物标志物，它可能有潜力成为PTC诊断及LN状态评估的非侵入性血液生物标志物。
