Zhu Tao, Gao Wen, Chen Xi, Zhang Ying, Wu Meijuan, Zhang Ping, Wang Shihua
*Department of Gynecologic Oncology, †Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China; and ‡Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC.
Int J Gynecol Cancer. 2017 Jan;27(1):3-10. doi: 10.1097/IGC.0000000000000846.
Early diagnosis of epithelial ovarian cancer is critical for patient survival. The objective of this pilot study is to identify a circulating micro (mi)RNA as a potential biomarker for epithelial ovarian cancer.
A total of 135 epithelial ovarian cancer patients and 54 benign ovarian tumor patients were recruited for this study. Using customized TaqMan low density miRNA arrays, we first screened expression levels of 48 miRNAs in sera from 18 epithelial ovarian cancer patients and 16 benign ovarian tumor patients. The most significantly and differentially expressed miRNA was then further examined in all serum samples using real-time polymerase chain reaction. Its expression was further analyzed in relationship with clinicopathological factors and patient survival.
Array screening data showed that expression levels of serum miRNA-20a, miRNA-125b, miRNA-126, miRNA-355, and let-7c were significantly different between malignant and benign ovarian tumor patients. Subsequent real-time polymerase chain reaction results showed that serum miRNA-125b levels were significantly higher in epithelial ovarian cancer patients compared to benign controls. Moreover, serum miRNA-125b levels were significantly higher in ovarian cancer patients in early stages I and II, and in patients having no residual tumor following surgery, but were not associated with differentiation and histological types of ovarian cancer. Notably, the higher level of miR-125b was significantly positively correlated with progression-free survival (P = 0.035) and marginally, with overall survival (P = 0.069).
miRNA-125b plays an important role in the pathogenesis and progression of epithelial ovarian cancer. Circulating miRNA-125b has the potential to become a novel biomarker for early diagnosis and prognosis prediction of epithelial ovarian cancer.
上皮性卵巢癌的早期诊断对患者生存至关重要。本初步研究的目的是鉴定一种循环微小（mi）RNA作为上皮性卵巢癌的潜在生物标志物。
本研究共招募了135例上皮性卵巢癌患者和54例良性卵巢肿瘤患者。使用定制的TaqMan低密度miRNA芯片，我们首先筛选了18例上皮性卵巢癌患者和16例良性卵巢肿瘤患者血清中48种miRNA的表达水平。然后使用实时聚合酶链反应在所有血清样本中进一步检测差异最显著的miRNA的表达。进一步分析其表达与临床病理因素及患者生存的关系。
芯片筛选数据显示，恶性和良性卵巢肿瘤患者血清miRNA-20a、miRNA-125b、miRNA-126、miRNA-355和let-7c的表达水平存在显著差异。随后的实时聚合酶链反应结果显示，上皮性卵巢癌患者血清miRNA-125b水平显著高于良性对照。此外，I期和II期早期卵巢癌患者以及术后无残留肿瘤患者的血清miRNA-125b水平显著更高，但与卵巢癌的分化和组织学类型无关。值得注意的是，较高水平的miR-125b与无进展生存期显著正相关（P = 0.035），与总生存期呈边缘正相关（P = 0.069）。
miRNA-125b在上皮性卵巢癌的发病机制和进展中起重要作用。循环miRNA-125b有可能成为上皮性卵巢癌早期诊断和预后预测的新型生物标志物。
