ITGA2基因在胰腺癌中表达和临床意义的生物信息学分析

Bioinformatics analysis of the expression and clinical significance of ITGA2 gene in pancreatic adenocarcinoma

摘要:

目的： 通过生物信息学方法研究ITGA2（integrin alpha-2）基因在胰腺癌中的表达情况、表达与预后的关系、表达与临床病理特征的关系，并进一步预测ITGA2的生物学功能。方法： 使用GEPIA在线工具分析肿瘤基因组图谱（The Cancer Genome Atlas，TCGA）中ITGA2基因在胰腺癌组织和正常组织中的表达差异，并回顾性分析表达水平与生存预后的关系。利用LinkedOmics数据库筛选ITGA2在胰腺癌中的共表达基因列表，在WebGestalt数据库中分析生物学功能。下载TCGA数据库中胰腺癌患者临床信息和ITGA2表达数据，分析ITGA2表达量与临床病理特征的关系，研究影响胰腺癌生存预后的危险因素。结果： ITGA2在胰腺癌组织中显著高表达（P<0.05）；与低表达患者相比，ITGA2高表达的胰腺癌患者的总体生存期（log-rank P=0.002）、无病生存期（log-rank P=0.004）明显降低。利用LinkedOmics找出278个与ITGA2共表达的基因，GO分析显示这些基因主要参与细胞黏附、细胞间连接组成、细胞骨架形成等生物过程；KEGG分析显示显著富集于黏着斑、黏附连接、紧密连接、肌动蛋白细胞骨架的调节、肿瘤蛋白聚糖等通路。ITGA2表达水平与肿瘤分期（χ²=6.380，P=0.036）、肿瘤大小或侵袭范围（χ²=5.214，P=0.022）、肿瘤分化程度（χ²=11.998，P=0.002）显著相关具有统计学意义。Cox回归分析结果显示，ITGA2表达水平是影响胰腺癌患者预后的独立危险因素（HR=1.888，95%CI=1.021~3.490，P=0.043）。结论： ITGA2基因与胰腺癌发生发展密切相关，可作为临床判定胰腺癌预后的标志物，并有成为肿瘤治疗靶点的潜力。

Abstract:

Objective: To study the expression of ITGA2 (integrin alpha-2) in pancreatic adenocarcinoma, the relationship between expression and prognosis, the relationship between expression and clinicopathological characteristics, and to further predict the biological function of ITGA2. Methods: The GEPIA online tool was used to analyze the expression difference of ITGA2 gene in pancreatic adenocarcinoma tissues and normal tissues in The Cancer Genome Atlas (TCGA) database, and the relationship between the expression level and survival prognosis was analyzed retrospectively. The LinkedOmics database was used to screen the list of co-expressed genes of ITGA2 in pancreatic adenocarcinoma, and the biological functions were analyzed in the WebGestalt database. The clinical information and ITGA2 expression data of pancreatic adenocarcinoma patients was downloaded, the relationship between ITGA2 expression and clinicopathological characteristics was analyzed, and the risk factors that would affect survival and prognosis of pancreatic adenocarcinoma was studied. Results: ITGA2 was significantly highly expressed in pancreatic adenocarcinoma tissues (P<0.05). Compared with patients with low expression, the overall survival of pancreatic adenocarcinoma patients with high ITGA2 expression (log-rank P=0.002) and disease-free survival (log-rank P=0.004) significantly reduced. Using LinkedOmics, 278 genes co-expressed with ITGA2 were identified. Gene Ontology (GO) analysis showed that these genes were mainly involved in biological processes such as cell adhesion, intercellular junction composition, and cytoskeleton formation; Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed significant enrichment in focal adhesions, adhesion junctions, tight junctions, regulation of actin cytoskeleton, tumor proteoglycans and other pathways. The expression level of ITGA2 was significantly correlated with tumor stage (χ²=6.380, P=0.036) , tumor size or invasion range (χ²=5.214, P=0.022) , and degree of tumor differentiation (χ²=11.998, P=0.002). Cox regression analysis showed that the expression level of ITGA2 was an independent risk factor affecting the prognosis of patients with pancreatic cancer (HR=1.888, 95%CI=1.021-3.490, P=0.043). Conclusion: ITGA2 gene is closely related to the occurrence and development of pancreatic adenocarcinoma, which can be used as a clinical marker to determine the prognosis of pancreatic adenocarcinoma and has the potential to become a tumor treatment target.