Zhou You, Zheng Xiao, Xu Bin, Hu Wenwei, Huang Tao, Jiang Jingting
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China.
Front Genet. 2019 Aug 21;10:751. doi: 10.3389/fgene.2019.00751. eCollection 2019.
Ovarian cancer is one of the leading causes of cancer mortality in women. Since little clinical symptoms were shown in the early period of ovarian cancer, most patients were found in phases III-IV or with abdominal metastasis when diagnosed. The lack of effective early diagnosis biomarkers makes ovarian cancer difficult to screen. However, in essence, the fundamental problem is we know very little about the regulatory mechanisms during tumorigenesis of ovarian cancer. There are emerging regulatory factors, such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), which have played important roles in cancers. Therefore, we analyzed the RNA-seq profiles of 407 ovarian cancer patients. An integrative network of 20,424 coding RNAs (mRNAs), 10,412 lncRNAs, and 742 miRNAs were construed with variance inflation factor (VIF) regression method. The mRNA-lncRNA-miRNA cliques were identified from the network and analyzed. Such promising cliques showed significant correlations with survival and stage of ovarian cancer and characterized the complex sponge regulatory mechanism, suggesting their contributions to tumorigenicity. Our results provided novel insights of the regulatory mechanisms among mRNAs, lncRNAs, and miRNAs and highlighted several promising regulators for ovarian cancer detection and treatment.
卵巢癌是女性癌症死亡的主要原因之一。由于卵巢癌早期临床症状不明显,大多数患者在诊断时已处于III-IV期或发生了腹部转移。缺乏有效的早期诊断生物标志物使得卵巢癌难以筛查。然而,从本质上讲,根本问题是我们对卵巢癌肿瘤发生过程中的调控机制了解甚少。有一些新兴的调控因子,如长链非编码RNA(lncRNA)和微小RNA(miRNA),它们在癌症中发挥了重要作用。因此,我们分析了407例卵巢癌患者的RNA测序图谱。采用方差膨胀因子(VIF)回归方法构建了一个包含20424个编码RNA(mRNA)、10412个lncRNA和742个miRNA的整合网络。从该网络中识别并分析了mRNA-lncRNA-miRNA团块。这些有前景的团块与卵巢癌的生存率和分期显著相关,并表征了复杂的海绵调控机制,表明它们对肿瘤发生的作用。我们的结果为mRNA、lncRNA和miRNA之间的调控机制提供了新的见解,并突出了几个有前景的用于卵巢癌检测和治疗的调控因子。