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鉴定结直肠癌四个阶段相关的基因:基因表达谱分析。

Identification of genes involved in the four stages of colorectal cancer: Gene expression profiling.

机构信息

Tianjin Union Medical Center, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, PR China.

Tianjin Union Medical Center, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, PR China; School of Chemical Engineering and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, PR China.

出版信息

Mol Cell Probes. 2018 Feb;37:39-47. doi: 10.1016/j.mcp.2017.11.004. Epub 2017 Nov 24.

Abstract

BACKGROUND

Colorectal cancer (CRC) is a common cancer with high morbidity and mortality. However, its molecular mechanism is not clear, nor the genes related to CRC stages.

METHODS

Gene expression data in CRC and healthy colorectal tissues were obtained from gene expression omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between control and CRC (stage I, II, III, and IV), obtaining 4 DEG sets. VennPlex was utilized to find all DEGs and intersection DEGs. Functional interactions between all DEGs and protein-protein interactions (PPIs) between intersection DEGs were analyzed using ReactomeFIViz and STRING, respectively, and networks were visualized. Known CRC-related genes were down-loaded from Comparative Toxicogenomics Database and mapped to PPI network.

RESULTS

Totally, 851, 760, 729, and 878 DEGs were found between control and CRC stage I, II, III, and IV, respectively. Taken together, 1235 DEGs were found, as well as 128 up-regulated intersection DEGs, 365 down-regulated intersection DEGs, and 0 contra-regulated DEG. A functional interaction network of all DEGs and a PPI network of intersection DEGs were constructed, in which CDC20, PTTG1, and MAD2L1 interacted with BUB1B; UGT2B17 interacted with ADH1B; MCM7 interacted with MCM2. BUB1B, ADH1B, and MCM2 were known CRC-related genes. Gradually upregulated expressions of CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 in stage I, II, III, and IV CRC were confirmed by using quantitative PCR. Besides, up-regulated intersection DEGs enriched in pathways about Cell cycle, DNA replication, and p53 signaling.

CONCLUSION

CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 might be CRC stage-related genes.

摘要

背景

结直肠癌(CRC)是一种发病率和死亡率都很高的常见癌症。然而,其分子机制尚不清楚,也没有与 CRC 分期相关的基因。

方法

从基因表达综合数据库中获取 CRC 和健康结直肠组织的基因表达数据。使用 Limma 包识别对照和 CRC(I 期、II 期、III 期和 IV 期)之间的差异表达基因(DEGs),获得 4 个 DEG 集。使用 VennPlex 找到所有 DEGs 和交集 DEGs。使用 ReactomeFIViz 和 STRING 分别分析所有 DEGs 的功能相互作用和交集 DEGs 的蛋白质-蛋白质相互作用(PPIs),并可视化网络。从比较毒理学基因组数据库下载已知的 CRC 相关基因,并映射到 PPI 网络。

结果

分别在对照和 CRC Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期中发现 851、760、729 和 878 个 DEGs。综合起来,发现了 1235 个 DEGs,以及 128 个上调的交集 DEGs、365 个下调的交集 DEGs和 0 个 contra-regulated DEG。构建了所有 DEGs 的功能相互作用网络和交集 DEGs 的 PPI 网络,其中 CDC20、PTTG1 和 MAD2L1 与 BUB1B 相互作用;UGT2B17 与 ADH1B 相互作用;MCM7 与 MCM2 相互作用。BUB1B、ADH1B 和 MCM2 是已知的 CRC 相关基因。通过定量 PCR 证实,CDC20、PTTG1、MAD2L1、UGT2B17 和 MCM7 在 I、II、III 和 IV 期 CRC 中逐渐上调表达。此外,上调的交集 DEGs 富集在细胞周期、DNA 复制和 p53 信号通路中。

结论

CDC20、PTTG1、MAD2L1、UGT2B17 和 MCM7 可能是与 CRC 分期相关的基因。

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