Cao Qing, Lu Kunlin, Dai Suiping, Hu Yan, Fan Weifang
Department of Obstetrics and Gynecology, The 180th Hospital of Chinese People's Liberation Army Hua-Yuan Road No.180, Quanzhou City, Fujian Province, 362000 China.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):2392-401. eCollection 2014.
The aim of the present study was to investigate the association of the expression of members in the miR-200 family with clinicopathological characteristics and their impacts on overall survival in patients with epithelial ovarian cancer (EOC). Expression levels of members in the miR-200 family, including miR-200a, miR-200b, miR-200c, miR-141, and miR-429, were detected by using miRNA qRT-PCR and in situ hybridization. Associations of their expression with clinicopathological factors and overall survival were statistically evaluated. Among five members in the miR-200 family, the expression levels of miR-200a, miR-200b and miR-200c were significantly higher in EOC tissues than those in normal surface ovarian epithelium tissues, in line with the findings ofin situ hybridization analysis. In addition, tumors with high miR-200a and miR-200 bexpressionwere both more likely to have advanced stage (both P=0.006) and higher grade (P=0.01 and 0.02), whilehighmiR-200 cexpression was onlysignificantly associated with advanced stage disease (P=0.01). Moreover, univariate analysis showed that the patients with high miR-200a, miR-200b and miR-200c expression all correlated with shorter overall survival in EOC patients (all P<0.001). Multivariate statistical analysis further identified miR-200a, miR-200b and miR-200c asindependent prognostic factorsfor EOC (all P=0.01). In conclusion, these findings suggest that miR-200a, miR-200b and miR-200c overexpression may promote the aggressive tumor progression and be recognized as reliable markers to predict the survival in patients with EOCs. The three miRNAs could be attractive therapeutic targets in patients with advanced-stage EOCs.
本研究的目的是探讨miR-200家族成员的表达与上皮性卵巢癌(EOC)患者临床病理特征的相关性及其对总生存期的影响。采用miRNA qRT-PCR和原位杂交技术检测miR-200家族成员,包括miR-200a、miR-200b、miR-200c、miR-141和miR-429的表达水平。对其表达与临床病理因素及总生存期的相关性进行统计学评估。在miR-200家族的五个成员中,EOC组织中miR-200a、miR-200b和miR-200c的表达水平显著高于正常卵巢表面上皮组织,这与原位杂交分析结果一致。此外,miR-200a和miR-200b高表达的肿瘤都更有可能处于晚期(P均=0.006)且分级更高(P=0.01和0.02),而miR-200c高表达仅与晚期疾病显著相关(P=0.01)。此外,单因素分析显示,miR-200a、miR-200b和miR-200c高表达的患者在EOC患者中的总生存期均较短(P均<0.001)。多因素统计分析进一步确定miR-200a、miR-200b和miR-200c为EOC的独立预后因素(P均=0.01)。总之,这些发现表明,miR-200a、miR-200b和miR-200c的过表达可能促进肿瘤的侵袭性进展,并被认为是预测EOC患者生存的可靠标志物。这三种miRNA可能是晚期EOC患者有吸引力的治疗靶点。