基于生物信息学分析的原发性结直肠癌新型生物标志物和发病机制的研究进展。

Insights regarding novel biomarkers and the pathogenesis of primary colorectal carcinoma based on bioinformatic analysis.

机构信息

Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China.

Department of Neurology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China.

出版信息

Comput Biol Chem. 2020 Apr;85:107229. doi: 10.1016/j.compbiolchem.2020.107229. Epub 2020 Feb 4.

DOI:10.1016/j.compbiolchem.2020.107229

PMID:32058945

Abstract

BACKGROUND

Biomarkers are important in the study of tumor processes for early detection and precise treatment. The biomarkers that have been previously detected are not useful for clinical application for primary colorectal carcinoma (PCRC). The aim of this study was to explore clinically valuable biomarkers of PCRC based on integrated bioinformatic analysis.

MATERIAL AND METHODS

Gene expression data were acquired from the GSE41258 dataset, and the differentially expressed genes were determined between PCRC and normal colorectal samples. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were implemented via Gene Set Enrichment Analysis. A protein-protein interaction (PPI) network was constructed. The significant modules and hub genes were screened and identified in the PPI network.

RESULTS

A total of 202 DEGs were identified, including 58 upregulated and 144 downregulated genes in PCRC samples compared to those in normal colorectal samples. Enrichment analysis demonstrated that the gene sets enriched in PCRC were significantly related to bicarbonate transport, regulation of sodium ion transport, potassium ion homeostasis, regulation of telomere maintenance, and other processes. A total of 10 hub genes was identified by cytoHubba: PYY, CXCL3, CXCL11, CXCL8, CXCL12, CCL20, MMP3, P2RY14, NPY1R, and CXCL1.

CONCLUSION

The hub genes, such as NPY1R, P2RY14, and CXCL12, and the electrolyte disequilibrium resulting from the differential expression of genes, especially bicarbonate imbalance, may provide novel insights and evidence for the future diagnosis and targeted therapy of PCRC.

摘要

背景

生物标志物在肿瘤研究中对于早期检测和精准治疗非常重要。然而，先前检测到的生物标志物对于原发性结直肠癌（PCRC）的临床应用并不实用。本研究旨在通过综合生物信息学分析，探索具有临床价值的 PCRC 生物标志物。

材料与方法

从 GSE41258 数据集获取基因表达数据，确定 PCRC 与正常结直肠样本之间的差异表达基因。通过基因集富集分析（Gene Set Enrichment Analysis，GSEA）进行基因本体论（Gene Ontology，GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）分析。构建蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络。筛选和鉴定 PPI 网络中的显著模块和枢纽基因。

结果

共鉴定出 202 个差异表达基因，其中 PCRC 样本中 58 个上调，144 个下调。富集分析表明，PCRC 中富集的基因集与碳酸氢盐转运、钠离子转运调节、钾离子稳态调节、端粒维持调节等过程显著相关。通过 cytoHubba 鉴定出 10 个枢纽基因：PYY、CXCL3、CXCL11、CXCL8、CXCL12、CCL20、MMP3、P2RY14、NPY1R 和 CXCL1。