Qi Chong, Hong Liang, Cheng Zhijian, Yin Qingzhang
Department of General Surgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, P.R. China.
Oncol Lett. 2016 Jan;11(1):568-574. doi: 10.3892/ol.2015.3956. Epub 2015 Nov 23.
The aim of the present study was to detect the candidate genes involved in the metastasis of colorectal cancer (CRC). Gene expression profiles of primary and metastatic CRC samples in the GSE14297 and GSE49355 datasets were downloaded from the Gene Expression Omnibus database. Subsequent to processing, Fishers exact test and the metaDE package in R language were applied to screen the differentially expressed genes (DEGs) between primary and metastatic CRC samples. In addition, function and pathway enrichment analysis was performed using online tools in the Database for Annotation, Visualization, and Integrated Discovery resource and common DEGs in GSE14297 and GSE49355 were identified. Their expression values in another dataset, GSE29621, were then collected in order to screen the genes with high standard deviations between primary and metastatic samples, which were considered as candidate metastasis-associated genes. Candidate genes were finally verified by performing survival analysis via the log-rank test. A total of 370 DEGs were screened in GSE14297 and GSE49355, and 77 common DEGs were identified. Upregulated DEGs were mainly enriched in the immune, energy metabolism and drug metabolism-associated functions. Downregulated DEGs were mainly enriched in cell adhesion-associated functions. A total of 12 genes, including the carbonic anhydrase II (), carcinoembryonic antigen-related cell adhesion molecule 7 (), Fc fragment of immunoglobulin G binding protein (), and placenta-specific 8 (), were the candidate metastasis-associated genes, among which expression significantly decreased the overall survival time of patients. The selected candidate metastasis-associated gene, , may be used as a potential therapeutic target in patients with metastatic CRC.
本研究的目的是检测参与结直肠癌(CRC)转移的候选基因。从基因表达综合数据库下载了GSE14297和GSE49355数据集中原发性和转移性CRC样本的基因表达谱。经过处理后,应用Fisher精确检验和R语言中的metaDE包筛选原发性和转移性CRC样本之间的差异表达基因(DEG)。此外,使用注释、可视化和综合发现数据库资源中的在线工具进行功能和通路富集分析,并鉴定GSE14297和GSE49355中的常见DEG。然后收集它们在另一个数据集GSE29621中的表达值,以筛选原发性和转移性样本之间具有高标准偏差的基因,这些基因被视为候选转移相关基因。最后通过对数秩检验进行生存分析来验证候选基因。在GSE14297和GSE49355中总共筛选出370个DEG,并鉴定出77个常见DEG。上调的DEG主要富集在免疫、能量代谢和药物代谢相关功能中。下调的DEG主要富集在细胞粘附相关功能中。共有12个基因,包括碳酸酐酶II、癌胚抗原相关细胞粘附分子7、免疫球蛋白G结合蛋白的Fc片段和胎盘特异性8,是候选转移相关基因,其中的表达显著降低了患者的总生存时间。所选的候选转移相关基因可能用作转移性CRC患者的潜在治疗靶点。