The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma
The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma
复制标题
食管鳞癌中胶原蛋白家族基因表达的临床意义
DOI：
10.7717/peerj.7705
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发表时间：
2019-10-04
期刊：
影响因子：
2.7
通讯作者：
Wang, Shaoxiang
中科院分区：
文献类型：
--
作者：
Li, Jieling;Wang, Xiao;Wang, Shaoxiang
背景：食管鳞状细胞癌（ESCC）是食管癌的一个亚型，发病率和死亡率都很高。由于ESCC患者的5年生存率很低，因此探索早期ESCC的新诊断标志物是迫切的。胶原是细胞外基质的丰富成分，在肿瘤生长和上皮-间质转化中起关键作用。然而，胶原基因在食管鳞癌中的临床意义却很少被研究。本研究系统分析了ESCC中胶原蛋白家族的基因表达，旨在寻找理想的生物标志物。方法：收集ESCC患者的临床资料和基因表达谱，数据来自The Cancer Genome Atlas和基因表达综合数据库。采用差异表达分析、生存分析、基因集富集分析（GSEA）和共表达网络分析等生物信息学方法，对44个胶原蛋白家族基因的表达模式与食管鳞癌发生发展的关系进行研究。其中，COL 1A 1、COL 10A 1和COL 11 A1在食管鳞癌组织中表达显著上调，COL 4A 4、COL 6A 5和COL 14 A1表达显著下调。COL 6A 5低表达或COL 18 A1高表达的患者生存率低。此外，建立了基于胶原基因表达的7基因预测模型来预测患者的生存期，该模型的预测准确性优于基于肿瘤淋巴结转移分期的模型。GSEA结果提示胶原基因可能与PI 3 K/Akt/mTOR通路、p53通路、细胞凋亡、细胞周期等密切相关。结论：几种胶原基因可能是食管鳞癌诊断和预后的潜在生物标志物。此外，一种新的7基因预测模型可能有助于预测ESCC患者的生存结局。这些发现可能有助于早期发现ESCC，并有助于改善患者的预后。
Background: Esophageal squamous cell carcinoma (ESCC) is a subtype of esophageal cancer with high incidence and mortality. Due to the poor 5-year survival rates of patients with ESCC, exploring novel diagnostic markers for early ESCC is emergent. Collagen, the abundant constituent of extracellular matrix, plays a critical role in tumor growth and epithelial-mesenchymal transition. However, the clinical significance of collagen genes in ESCC has been rarely studied. In this work, we systematically analyzed the gene expression of whole collagen family in ESCC, aiming to search for ideal biomarkers.Methods: Clinical data and gene expression profiles of ESCC patients were collected from The Cancer Genome Atlas and the gene expression omnibus databases. Bioinformatics methods, including differential expression analysis, survival analysis, gene sets enrichment analysis (GSEA) and co-expression network analysis, were performed to investigate the correlation between the expression patterns of 44 collagen family genes and the development of ESCC.Results: A total of 22 genes of collagen family were identified as differentially expressed genes in both the two datasets. Among them, COL1A1, COL10A1 and COL11A1 were particularly up-regulated in ESCC tissues compared to normal controls, while COL4A4, COL6A5 and COL14A1 were notably down-regulated. Besides, patients with low COL6A5 expression or high COL18A1 expression showed poor survival. In addition, a 7-gene prediction model was established based on collagen gene expression to predict patient survival, which had better predictive accuracy than the tumor-node-metastasis staging based model. Finally, GSEA results suggested that collagen genes might be tightly associated with PI3K/Akt/mTOR pathway, p53 pathway, apoptosis, cell cycle, etc.Conclusion: Several collagen genes could be potential diagnostic and prognostic biomarkers for ESCC. Moreover, a novel 7-gene prediction model is probably useful for predicting survival outcomes of ESCC patients. These findings may facilitate early detection of ESCC and help improves prognosis of the patients.