Mosapour Abbas, Karami Tehrani Fatemeh Soghra, Atri Morteza
Cancer Research Lab, Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Surgery, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2020 Aug;23(8):1045-1052. doi: 10.22038/ijbms.2020.44581.10421.
MicroRNAs (miRs) are a class of small non-coding RNAs which are associated with tumor growth and progression. In the present study, we assessed the expression of selected miRs in malignant, benign, and adjacent normal breast tissues.
The expression of miR-1297, miR-3191-5P, miR-4435, and miR-4465 were evaluated in malignant (n=50), benign (n=35), and adjacent normal breast tissues (n=20) using qRT-PCR. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were generated for evaluating the diagnostic values of miRs. To evaluate diagnostic efficacy, miRs-based score was obtained using the logistic regression model.
Among malignant tumors, the expression of miR-1297, miR-3191-5p, and miR-4435 was significantly lower (=0.024, <0.001 and =0.031), respectively. The expression of miR-4465 was higher (=0.023) than that of normal tissue. The expression of these miRs was lower than those of benign tumors (<0.01, <0.001, <0.0001, and <0.01, respectively). We observed a positive correlation between miR-4465 expression levels and tumor stage (=0.042) and a negative correlation with grade and Ki-67 score (<0.05). The AUCs for miR-1297, miR-3191-5p, miR-4435, and miR-4465 in malignant tumors versus normal tissues were 0.784, 0.700, 0.976, and 0.865 and versus benign tumors they were 0.938, 0.857, 0.981, and 0.785, respectively. The optimal logit(P) value of 0.262 distinguished malignant from normal subjects with a sensitivity of 0.91, specificity of 0.85, and an overall accuracy of 0.89.
The panel of these miRs are suggested as possible onco-miRs(miR-4465) or tumor suppressor-miRs (miR-3191-5P, miR-1297, miR-4435). Overall, our results indicated that these miRs could be introduced as diagnostic biomarkers in breast cancer patients.
微小RNA(miR)是一类与肿瘤生长和进展相关的小非编码RNA。在本研究中,我们评估了特定miR在恶性、良性及相邻正常乳腺组织中的表达。
采用qRT-PCR检测了50例恶性乳腺组织、35例良性乳腺组织及20例相邻正常乳腺组织中miR-1297、miR-3191-5P、miR-4435和miR-4465的表达。绘制受试者工作特征(ROC)曲线及ROC曲线下面积(AUC)以评估miR的诊断价值。为评估诊断效能,使用逻辑回归模型获得基于miR的评分。
在恶性肿瘤中,miR-1297、miR-3191-5p和miR-4435的表达分别显著降低(P=0.024、P<0.001和P=0.031)。miR-4465的表达高于正常组织(P=0.023)。这些miR的表达低于良性肿瘤(分别为P<0.01、P<0.001、P<0.0001和P<0.01)。我们观察到miR-4465表达水平与肿瘤分期呈正相关(P=0.042),与分级和Ki-67评分呈负相关(P<0.05)。miR-1297、miR-3191-5p、miR-4435和miR-4465在恶性肿瘤与正常组织中的AUC分别为0.784、0.700、0.976和0.865,在恶性肿瘤与良性肿瘤中的AUC分别为0.938、0.857、0.981和0.785。最佳logit(P)值为0.262,区分恶性与正常受试者的灵敏度为0.91,特异度为0.85,总准确率为0.89。
这些miR被认为可能是癌miR(miR-4465)或抑癌miR(miR-3191-5P、miR-1297、miR-4435)。总体而言,我们的结果表明这些miR可作为乳腺癌患者的诊断生物标志物。