外泌体中多种miRNA/lncRNAs联合检测在卵巢癌早期诊断中临床价值研究

Ovarian cancer is the second most common female malignant tumor, which is also the most deadly malignant tumor in the female reproductive system. There is stil a lack of effective diagnostic methods of ovarian cancer for several reasons,such as insidious onset;often asymptomatic before metastasis which makes it more difficult for early discovery;and there is no specific markers. Although the early detection methods for ovarian cancer include gynecological pelvic examination, serological markers examination, imaging examination and combined application of these detection methods. Ovarian cancer still can not be diagnosed in the early stage because of the limitations of their low sensitivity and specificity. Therefore, it is necessary to screen more sensitive and specific biomarker for early detection of ovarian cancer.The study found that the lncRNA:H19, HOTAIR, PVT1, DNM3OS, DNM3OS and ovarian cancer were related to the early development of ovarian cancer.Our previous studies also found that miRNA:HER2、SOCS3 and STAT 3 were expressed in different degrees in the early development of ovarian cancer.In this study,we clarify the expression and regulation mechanism in ovarian tumor microenvironment of exosomes miRNA/LncRNA which is derived from tumor cells.Then we build miRNA/LncRNA panel, combine multiple miRNA/LncRNA, add a joint algorithm, and weigh different miRNA/LncRNA. Finally, the optimization algorithm is applied to the detection and early diagnosis of ovarian cancer. The method can improve the early diagnosis of ovarian cancer, improve the survival rate of patients, and help earlier clinical treatment.It also helps to determine whether women have retained fertility.

卵巢癌是女性中第二常见的妇科恶性肿瘤，目前还没有敏感性和特异性均较高的单一标志物，迄今为止仍缺乏有效的早期诊断方法。研究发现与卵巢癌相关的lncRNA：BCYRNI、H19、HOTAIR、PVT1、DNM3OS与卵巢癌早期发生发展密切相关。我们前期研究也发现HER2、SOCS3和STAT3的miRNA在卵巢癌的早期发生发展中呈不同程度的表达。但卵巢癌相关微小核糖核酸/长链非编码RNA(miRNA/LncRNA)在卵巢癌发生发展中的作用目前尚不清晰。本研究拟通过研究肿瘤来源的miRNA/LncRNA在卵巢肿瘤微环境中表达调控作用，通过构建miRNA/LncRNA组合，联合多种miRNA/LncRNA，对不同的miRNA/LncRNA进行加权模型计算，从而应用于卵巢癌的早期诊断。提高卵巢癌的早期诊断水平，就能提升患者生存率，同时也有助于判断年轻患者是否具有保留生育功能。

癌症免疫治疗已经成为一种有前途的肿瘤治疗方法，它激活免疫系统以诱导肿瘤免疫监视或逆转肿瘤免疫逃逸的占有特性。卵巢癌（OC）是最致命的妇科恶性肿瘤，它正在激活免疫系统以诱导肿瘤免疫监视或逆转肿瘤免疫逃逸的占有特性。然而，"免疫逃逸 "已经导致了多项临床研究的失败。当肿瘤细胞出现时，宿主的免疫系统会做出反应，而中性粒细胞是抵御感染的第一道防线。生物信息学预测确定了lncRNA HOTTIP和IL-6之间的竞争位点，IL-6是中性粒细胞运输炎症反应的一个关键检查点调节器，调节趋化因子的合成并与白细胞死亡有关。已知当IL-6存在时，STAT3信号通路可上调耐受性抗原呈递细胞中的PD-L1表达。通过与淋巴细胞上的PD-1受体结合，PD-L1会降低宿主免疫力，增加腹膜扩散，使OC恶化。根据前面的事实，我们提出了HOTTIP通过调节IL-6和PD影响OC的观点。HOTTIP被认为是通过调控IL-6和PD-L1来影响OC。在前期工作中，我们发现HER2、SOCS3和STAT3的miRNAs在卵巢癌的早期阶段有不同的表达。然而，卵巢癌相关的外泌体miRNA/LncRNA在卵巢癌发生中的意义仍然未知。通过构建miRNA/LncRNA组合，结合多种miRNA/LncRNA，并对不同的miRNA/LncRNA进行加权模型计算，我们希望研究肿瘤外泌体miRNA/LncRNA在卵巢肿瘤微环境中的表达调节作用，并将其应用于卵巢癌的早期诊断。改善卵巢癌的早期检测将提高患者的存活率，并有助于确定年轻患者是否保留生育功能。同时，这项研究拓展研究阴道微生态学在检测和治疗卵巢癌方面的治疗作用，以及阴道微生态在肿瘤预防和治疗方面的功能。