Zuberi Mariyam, Khan Imran, Gandhi Gauri, Ray P C, Saxena Alpana
Department of Biochemistry, Maulana Azad Medical College, New Delhi, 110002, India.
Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA.
Tumour Biol. 2016 Aug;37(8):11259-66. doi: 10.1007/s13277-016-4993-2. Epub 2016 Mar 7.
Epithelial ovarian cancer (EOC) is the most lethal cause of morbidity and mortality worldwide. miRNA deregulation evinces a remarkable role in ovarian cancer tumorigenesis. miRNA-199a (miR-199a) is known to be involved in cancer development and progression. Although miR-199a has been studied in various cell types, its correlation with clinicopathological features in EOC has not been documented. In this study, we identified the clinicopathological hallmarks which might be perturbed due to the downregulation of serum miR-199a in EOC. Seventy serum samples from histopathologically confirmed EOC patients and 70 controls were collected. Total RNA from serum was isolated by Trizol method, polyadenylated and reverse transcribed into cDNA. Expression level of miR-199a was detected by using miRNA qRT-PCR. Relative expression was determined with matched controls using U6 snRNA as reference. Level of miR-199a expression was compared with distinct clinicopathological features. Expression of miR-199a was found to be significantly downregulated in comparison with matched normal controls. The expression level of miR-199a was found to be significantly associated with tumor stage, lymph node metastasis, and distal metastasis. Receiver operating characteristic (ROC) curve for diagnostic potential yielded significant area under the curve (AUC) with a considerable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status, and survival. Our findings suggest that miR-199a downregulation might be a potential indicator for disease progression promoting the aggressive tumor progression and be identified as a diagnostic marker to predict the prognosis and survival in EOC patients.
上皮性卵巢癌(EOC)是全球发病和死亡的最致命原因。miRNA失调在卵巢癌肿瘤发生中起着显著作用。已知miRNA-199a(miR-199a)参与癌症的发展和进程。尽管miR-199a已在多种细胞类型中进行了研究,但其与EOC临床病理特征的相关性尚未见报道。在本研究中,我们确定了可能因EOC患者血清miR-199a下调而受到干扰的临床病理特征。收集了70例经组织病理学确诊的EOC患者的血清样本和70例对照样本。采用Trizol法从血清中分离总RNA,进行多聚腺苷酸化并逆转录成cDNA。使用miRNA qRT-PCR检测miR-199a的表达水平。以U6 snRNA为参照,与匹配的对照样本比较确定相对表达量。将miR-199a的表达水平与不同的临床病理特征进行比较。发现与匹配的正常对照相比,miR-199a的表达明显下调。发现miR-199a的表达水平与肿瘤分期、淋巴结转移和远处转移显著相关。诊断潜力的受试者工作特征(ROC)曲线产生了显著的曲线下面积(AUC),具有相当高的敏感性和特异性。预后的ROC曲线在组织学分级、远处转移、淋巴结状态和生存率方面产生了显著的AUC。我们的研究结果表明,miR-199a下调可能是疾病进展的潜在指标,促进肿瘤的侵袭性进展,并可作为预测EOC患者预后和生存的诊断标志物。