Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Int J Med Sci. 2019 Sep 7;16(10):1338-1348. doi: 10.7150/ijms.38219. eCollection 2019.
Endometrial cancer is one of the most common cancers in women worldwide, affecting more than 300,000 women annually. Dysregulated gene expression, especially those mediated by microRNAs, play important role in the development and progression of cancer. This study aimed to investigate differentially expressed genes in endometrial adenocarcinoma using next generation sequencing (NGS) and bioinformatics. The gene expression profiles and microRNA profiles of endometrial adenocarcinoma (cancer part) and normal endometrial tissue (non-cancer part) were assessed with NGS. We identified 56 significantly dysregulated genes, including 47 upregulated and 9 downregulated genes, in endometrial adenocarcinoma. Most of these genes were associated with defense response, response to stimulus, and immune system process, and further pathway analysis showed that human papillomavirus infection was the most significant pathway in endometrial adenocarcinoma. In addition, these genes were also associated with decreased cell death and survival as well as increased cellular movement. The analyses using Human Protein Atlas, identified 6 genes (, , , , , and ) significantly associated with poorer prognosis and 3 genes (, , and ) significantly associated with better prognosis. Combining with the data of microRNA profiles using microRNA target predicting tools, two significantly dysregulated microRNA-mediated gene expression changes in endometrial adenocarcinoma were identified: downregulated hsa-miR-127-5p with upregulated and upregulated hsa-miR-218-5p with downregulated . These findings may contribute important new insights into possible novel diagnostic or therapeutic strategies for endometrial adenocarcinoma.
子宫内膜癌是全球女性最常见的癌症之一,每年影响超过 30 万名女性。基因表达失调,尤其是microRNA 介导的基因表达失调,在癌症的发生和发展中起着重要作用。本研究旨在通过下一代测序(NGS)和生物信息学研究,探讨子宫内膜腺癌中差异表达的基因。采用 NGS 评估子宫内膜腺癌(癌症部分)和正常子宫内膜组织(非癌症部分)的基因表达谱和 microRNA 谱。我们鉴定了 56 个在子宫内膜腺癌中显著失调的基因,包括 47 个上调基因和 9 个下调基因。这些基因大多与防御反应、对刺激的反应和免疫系统过程有关,进一步的通路分析表明,人乳头瘤病毒感染是子宫内膜腺癌中最重要的通路。此外,这些基因还与细胞死亡和存活减少以及细胞运动增加有关。使用 Human Protein Atlas 的分析,确定了 6 个与预后较差显著相关的基因(、、、、和)和 3 个与预后较好显著相关的基因(、和)。结合 microRNA 靶预测工具的 microRNA 图谱数据,我们鉴定了子宫内膜腺癌中两个显著失调的 microRNA 介导的基因表达变化:下调的 hsa-miR-127-5p 伴随着上调的和上调的 hsa-miR-218-5p 伴随着下调的。这些发现可能为子宫内膜腺癌的可能的新型诊断或治疗策略提供重要的新见解。