Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, People's Republic of China.
The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, 430071, People's Republic of China.
Dig Dis Sci. 2018 May;63(5):1219-1228. doi: 10.1007/s10620-018-4996-5. Epub 2018 Mar 1.
Human colon adenocarcinoma is one of the major causes of tumor-induced death worldwide. A complicated gene interconnection network significantly regulates its progression and prognosis. The aim of our study was to find hub genes associated with the progression and prognosis of colon adenocarcinoma and to illustrate the underlying mechanisms.
A weighted gene co-expression network analysis was performed in our study to identify significant gene modules and hub genes associated with the TNM stage of colon adenocarcinoma (n = 441).
In the turquoise module of interest, 23 hub genes were initially selected, and 10 of them were identified as "real" hub genes with high connectivity in the protein-protein interaction network. In the terms of validation, COL8A1 had the highest correlation with clinical traits among all of the hub genes. Data obtained from the Oncomine and GEPIA databases showed a higher expression of COL8A1 in colon adenocarcinoma tissues compared with normal colon tissues. Kaplan-Meier survival curves showed that higher expression of COL8A1 resulted in a shorter overall survival time and disease-free survival time. Univariate and multivariate Cox proportional hazards analyses indicated that the COL8A1 expression was an independent prognostic factor for survival in colon adenocarcinoma patients. Finally, gene set enrichment analysis indicated that the gene sets associated with focal adhesion were significantly enriched in colon adenocarcinoma samples with COL8A1 highly expressed.
COL8A1 was identified and proved to be correlated with the progression and prognosis of human colon adenocarcinoma, probably through regulating focal adhesion-related pathways.
人结肠腺癌是全球肿瘤相关死亡的主要原因之一。复杂的基因相互作用网络显著调节其进展和预后。我们研究的目的是寻找与结肠腺癌进展和预后相关的枢纽基因，并阐明其潜在机制。
在本研究中进行了加权基因共表达网络分析，以鉴定与结肠腺癌 TNM 分期相关的显著基因模块和枢纽基因（n=441）。
在所关注的绿松石模块中，最初选择了 23 个枢纽基因，其中 10 个基因在蛋白质-蛋白质相互作用网络中具有高连接性，被鉴定为“真正”的枢纽基因。在验证方面，COL8A1 在所有枢纽基因中与临床特征的相关性最高。来自 Oncomine 和 GEPIA 数据库的数据显示，COL8A1 在结肠腺癌组织中的表达高于正常结肠组织。Kaplan-Meier 生存曲线显示，COL8A1 表达水平较高的患者总生存期和无病生存期较短。单因素和多因素 Cox 比例风险分析表明，COL8A1 表达是结肠腺癌患者生存的独立预后因素。最后，基因集富集分析表明，在 COL8A1 高表达的结肠腺癌样本中，与粘着斑相关的基因集显著富集。
COL8A1 被鉴定并证明与人类结肠腺癌的进展和预后相关，可能通过调节粘着斑相关途径。
