Zuberi Mariyam, Khan Imran, Mir Rashid, Gandhi Gauri, Ray Prakash Chandra, Saxena Alpana
Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.
Department of Surgery, University of Illinois at Chicago, Chicago, Illinois, United States of America.
PLoS One. 2016 Apr 19;11(4):e0153902. doi: 10.1371/journal.pone.0153902. eCollection 2016.
MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan-Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.
微小RNA(miRNA)已被发现在上皮性卵巢癌(EOC)中表达失调,其可能作为肿瘤抑制基因(TSG)或癌基因发挥作用。miRNA的高甲基化会使其肿瘤抑制功能沉默,或者调节该miRNA的TSG发生高甲基化(反之亦然)会导致其功能丧失。本研究旨在评估异常的微小RNA - 125b(miR - 125b)表达对上皮性卵巢癌各种临床病理特征的影响及其与几种TSG异常甲基化的关联。我们纳入了70例新诊断的上皮性卵巢癌病例,记录了他们的临床病史,并纳入了70名健康女性志愿者。通过定量逆转录聚合酶链反应(qRT - PCR)测定血清miR - 125b水平,并通过甲基化特异性PCR研究各种TSG的甲基化状态。构建ROC曲线以评估miR - 125b的诊断和预后价值。应用Kaplan - Meier方法比较生存曲线。与健康对照相比,发现miR - 125b的表达显著上调(p<0.0001)。发现miR - 125b的表达水平与国际妇产科联盟(FIGO)分期、淋巴结和远处转移显著相关。诊断潜力的ROC曲线产生了具有相当敏感性和特异性的显著曲线下面积(AUC)。预后的ROC曲线在组织学分级、远处转移、淋巴结状态和生存方面产生了显著的AUC。miR - 125b的表达也与TSG的高甲基化显著相关。我们的结果表明,DNA高甲基化可能参与了miR - 125b的失活,并且miR - 125b可能作为EOC临床结局的潜在独立生物标志物。