Division of Genetics, Department of Biology, Faculty of Sciences, University of Isfahan, HezarJarib Street, Isfahan 81746-73441, Iran.
Division of Genetics, Department of Biology, Faculty of Sciences, University of Isfahan, HezarJarib Street, Isfahan 81746-73441, Iran.
Gene. 2019 Mar 1;687:272-279. doi: 10.1016/j.gene.2018.11.036. Epub 2018 Nov 20.
MicroRNAs are involved in diverse biological processes and their dysregulation is a common event in various diseases including breast cancer. Breast cancer is a major threat to women's health. This study was designed to examine the expression levels of miR-9 and miR-34a in breast tumor tissue samples and plasma of breast cancer patients, compare their expression pattern between tissue samples and plasma samples of patients and analyze their relationship with tumor clinical features. Also, the potential of these miRNAs as diagnostic biomarkers for breast cancer was investigated.
The expression levels of miR-9, miR-34a and CDH1 were measured by real-time reverse transcription polymerase chain reaction and ΔΔct method. Data were analyzed using t-test and one-way ANOVA. The sensitivity and specificity of miRNAs were determined by receiver operating characteristic (ROC) curve.
The expression levels of miR-9 and miR-34a were significantly down-regulated in tumor tissues compared to healthy tissues (fold change = 0.26, p = 0.0051 for miR-9 and fold change = 0.55, p = 0.021 for miR-34a). While no significant difference was observed in the expression levels of miR-9 (p = 0.205) and miR-34a (p = 0.132) in plasma samples of patients compared to normal plasma. CDH1 expression in tumor tissue was not significantly different from normal tissue (p = 0.33). We found that expression level of miR-9 in patients with tumor size larger than 5 cm (p = 0.026) and expression level of miR-34a in patients with higher stage (lll & lV, p = 0.03) were significantly down-regulated. Also miR-34a expression level was positively correlated with patient's age (p = 0.03).
According to the ROC curves, the area under the curve (AUC) of miR-9 in tissue was 0.71 (p = 0.009) with sensitivity 83.33% and specificity 70.37%. The AUC for miR-34a in tissue was 0.72 (p = 0.007) with sensitivity 72% and specificity 76%. Thus miR-9 and miR-34a have the capability for distinguishing tumor tissues from healthy tissues and the study of their expression levels in tissue may be used as a biomarker for the diagnosis of breast cancer patients from healthy women.
MicroRNAs 参与多种生物学过程，其失调是包括乳腺癌在内的各种疾病的常见事件。乳腺癌是对女性健康的主要威胁。本研究旨在检测乳腺癌患者肿瘤组织样本和血浆中 miR-9 和 miR-34a 的表达水平，比较患者组织样本和血浆样本中它们的表达模式，并分析它们与肿瘤临床特征的关系。此外，还研究了这些 miRNA 作为乳腺癌诊断生物标志物的潜力。
采用实时逆转录聚合酶链反应和 ΔΔct 法测定 miR-9、miR-34a 和 CDH1 的表达水平。采用 t 检验和单因素方差分析进行数据分析。通过接收者操作特征 (ROC) 曲线确定 miRNA 的灵敏度和特异性。
与健康组织相比，肿瘤组织中 miR-9 和 miR-34a 的表达水平明显下调（倍数变化分别为 0.26，p=0.0051 和 0.55，p=0.021）。而患者血浆样本中 miR-9 的表达水平无显著差异（p=0.205），miR-34a 的表达水平也无显著差异（p=0.132）。肿瘤组织中 CDH1 的表达与正常组织无显著差异（p=0.33）。我们发现，肿瘤大小大于 5cm 的患者 miR-9 的表达水平（p=0.026）和晚期（lll 和 lV 期）患者 miR-34a 的表达水平（p=0.03）显著下调。此外，miR-34a 的表达水平与患者年龄呈正相关（p=0.03）。
根据 ROC 曲线，组织中 miR-9 的曲线下面积（AUC）为 0.71（p=0.009），灵敏度为 83.33%，特异性为 70.37%。组织中 miR-34a 的 AUC 为 0.72（p=0.007），灵敏度为 72%，特异性为 76%。因此，miR-9 和 miR-34a 具有区分肿瘤组织与健康组织的能力，研究它们在组织中的表达水平可能可作为诊断乳腺癌患者与健康女性的生物标志物。
