卵巢癌血清相关miRNAs的筛选及其临床意义

Screening of mi RNAs in ovarian cancer patients and its correlation with clinicopathological features

背景与目的:卵巢癌预后较差,发现时通常是晚期,需找寻与卵巢癌发生、发展相关的诊治方法。该研究检测miRNA在上皮性卵巢癌患者术前外周血清及良性卵巢肿瘤患者外周血清中表达情况的差异,筛选差异有统计学意义的miRNA并分析其与上皮性卵巢癌患者临床病理特征、预后等的关系。方法:定制研究相关的48种miRNA表达谱芯片,通过Taq Man低密度微阵列芯片,筛选出有统计学意义的miRNA。采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)法验证筛选的miRNA在卵巢良、恶性肿瘤患者血清中的表达情况,选择具有统计学意义的miRNA行大样本验证并分析其与肿瘤分期、组织病理及预后等的关系。结果:通过Taq Man低密度微阵列芯片筛选和RTFQ-PCR验证,发现mi R-125b在上皮性卵巢癌患者血清中的表达高于良性肿瘤患者(P=0.039),mi R-125b在早期患者中的表达量高于晚期患者(P=0.003),术后无残余肿瘤患者表达量高于术后有残余肿瘤患者(P=0.013)。血清mi R-125b高表达有利于卵巢癌患者无进展生存期(progression-free survival,PFS)延长(P=0.003),但对总生存期(overall survival,OS)无明显影响(P=0.069)。结论:mi R-125b在上皮性卵巢癌的发生、发展中起着关键作用,与患者预后相关,是预测卵巢癌复发的潜在基因,但在肿瘤不同期别的表达情况发生变化,在早期作用比较明显,在晚期或肿瘤残余较多的患者表达较不明显,其作用机制有待进一步研究。

Background and purpose： The prognosis of ovarian cancer is poor and the diagnosis is relatively late. It is needed to search for early diagnosis and treatment for ovarian cancer. This study investigated the expression of serum miRNAs in patients with malignancy or benign ovarian tumor preoperativey and analyzed its correlation with clinicopathological progress and prognostic features of epithelial ovarian cancer. Methods： Forty-eight miRNAs which have been reported to be related to ovarian cancer were ordered. The differential expression of 48 miRNAs in the serum of patients with malignant or benign epithelial ovarian tumors was detected by TaqMan low density array. The differentially expressed miRNAs were further confirmed by real-time fluorescent quantitative polymerase chain reaction （RTFQ-PCR）. The relationship between the expression level of selected miRNA and clinical clinicopathological factors, progress and prognosis were analyzed. Results： TaqMan low density array and further RTFQ-PCR showed that only miR-125b was sig- nificantly increased in 135 ovarian cancer patients as compared with 38 individuals with benign tumor. The expression of miR-125b was higher in early stage patients than that in advanced stage patients （P=0.039）. The patients without residual tumor expressed more miR-125b than patients with residual tumor （P=0.013）. The high level of miR-125b was significantly correlated with longer progress free survival （PFS） （P=0.003）, but not correlated with overall survival （OS） （P=0.069）. Conclusion： MiR-125b may play an important role in the pathogenesis of epithelial ovarian cancer and prognosis. It may be a potential gene to predict the recurrence of epithelial ovarian cancer, but the change of gene expression at different stages and its underlying mechanism need further research.