Comprehensive analysis of differential co-expression patterns reveal transcriptional dysregulation mechanism and identify novel prognostic lncRNAs in esophageal squamous cell carcinoma.
Comprehensive analysis of differential co-expression patterns reveal transcriptional dysregulation mechanism and identify novel prognostic lncRNAs in esophageal squamous cell carcinoma.
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DOI：
10.2147/ott.s135312
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发表时间：
2017
影响因子：
4
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Li Z;Yao Q;Zhao S;Wang Y;Li Y;Wang Z
食管鳞状细胞癌（Esophageal squamous cell carcinoma，ESCC）是世界上最常见的恶性肿瘤之一，在中华人民共和国发病率较高。然而，ESCC的分子机制仍不清楚。在这项研究中，食管鳞癌的mRNA和长链非编码RNA（lncRNA）的表达谱从基因表达Omnibus数据库下载，然后差异共表达分析，以揭示改变的共表达关系的基因对在食管鳞癌肿瘤。共有3，709个mRNA和923个lncRNA在正常组织和肿瘤组织之间差异共表达，我们发现大多数基因对在肿瘤组织中失去了关联。差异调节网络的方法破译，转录失调普遍存在于食管鳞癌，和大多数差异调节环节的37个TF的调制。我们的研究还发现，两种新的lncRNA（ADAMTS 9-AS 1和AP000696.2）可能是外胚层和上皮细胞发育所必需的，它可以显著地将ESCC患者分为高风险和低风险组，并且比传统的临床肿瘤标志物要好得多。对两个危险组进一步检查发现，高危险组患者TF靶点调节的变化明显高于低危险组。此外，与两种lncRNA共表达的4种信号转导相关DCmRNA（ERBB 3、ENSA、KCNK 7、MFSD 5）也可能具有预测能力。我们的研究结果将从lncRNA和mRNA的交联角度加深对ESCC转录失调的理解，并且两种lncRNA的组合可能作为ESCC临床应用的新的预后生物标志物。
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide and occurs at a relatively high frequency in People’s Republic of China. However, the molecular mechanism underlying ESCC is still unclear. In this study, the mRNA and long non-coding RNA (lncRNA) expression profiles of ESCC were downloaded from the Gene Expression Omnibus database, and then differential co-expression analysis was used to reveal the altered co-expression relationship of gene pairs in ESCC tumors. A total of 3,709 mRNAs and 923 lncRNAs were differentially co-expressed between normal and tumor tissues, and we found that most of the gene pairs lost associations in the tumor tissues. The differential regulatory networking approach deciphered that transcriptional dysregulation was ubiquitous in ESCC, and most of the differentially regulated links were modulated by 37 TFs. Our study also found that two novel lncRNAs (ADAMTS9-AS1 and AP000696.2) might be essential in the development of ectoderm and epithelial cells, which could significantly stratify ESCC patients into high-risk and low-risk groups, and were much better than traditional clinical tumor markers. Further inspection of two risk groups showed that the changes in TF-target regulation in the high-risk patients were significantly higher than those in the low-risk patients. In addition, four signal transduction-related DCmRNAs (ERBB3, ENSA, KCNK7, MFSD5), which were differentially co-expressed with the two lncRNAs, might also have the predictive capacity. Our findings will enhance the understanding of ESCC transcriptional dysregulation from a view of cross-link of lncRNA and mRNA, and the two-lncRNA combination may serve as a novel prognostic biomarker for clinical applications of ESCC.