Liu Da, Qiu Min
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China.
Front Genet. 2021 Jun 24;12:673192. doi: 10.3389/fgene.2021.673192. eCollection 2021.
Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecologic malignancies, but only a few biomarkers have been proven to be effective in clinical practice. Previous studies have demonstrated the important roles of non-coding RNAs (ncRNAs) in diagnosis, prognosis, and therapy selection in UCEC and suggested the significance of integrating molecules at different levels for interpreting the underlying molecular mechanism. In this study, we collected transcriptome data, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs), of 570 samples, which were comprised of 537 UCEC samples and 33 normal samples. First, differentially expressed lncRNAs, miRNAs, and mRNAs, which distinguished invasive carcinoma samples from normal samples, were identified, and further analysis showed that cancer- and metabolism-related functions were enriched by these RNAs. Next, an integrated, dysregulated, and scale-free biological network consisting of differentially expressed lncRNAs, miRNAs, and mRNAs was constructed. Protein-coding and ncRNA genes in this network showed potential immune and metabolic functions. A further analysis revealed two clinic-related modules that showed a close correlation with metabolic and immune functions. RNAs in the two modules were functionally validated to be associated with UCEC. The findings of this study demonstrate an important clinical application for improving outcome prediction for UCEC.
子宫内膜癌(UCEC)是最常见的妇科恶性肿瘤之一,但在临床实践中仅有少数生物标志物被证明有效。先前的研究已证明非编码RNA(ncRNA)在UCEC的诊断、预后及治疗选择中发挥重要作用,并表明整合不同水平的分子对于阐释潜在分子机制具有重要意义。在本研究中,我们收集了570个样本的转录组数据,包括长链非编码RNA(lncRNA)、微小RNA(miRNA)和信使RNA(mRNA),其中包含537个UCEC样本和33个正常样本。首先,鉴定出区分浸润性癌样本与正常样本的差异表达lncRNA、miRNA和mRNA,进一步分析表明这些RNA富集了与癌症和代谢相关的功能。接下来,构建了一个由差异表达的lncRNA、miRNA和mRNA组成的整合、失调且无标度的生物网络。该网络中的蛋白质编码基因和ncRNA基因显示出潜在的免疫和代谢功能。进一步分析揭示了两个与临床相关的模块,它们与代谢和免疫功能密切相关。对这两个模块中的RNA进行功能验证,结果表明它们与UCEC相关。本研究结果证明了在改善UCEC预后预测方面的重要临床应用价值。