| 何光耀,牛佳乐,赵克晗,等.基于生物信息学分析整合素α 11在胃癌组织中的表达及临床意义[J].肿瘤学杂志,2025,31(10):865-871. |
| 基于生物信息学分析整合素α 11在胃癌组织中的表达及临床意义 |
| Bioinformatics Analysis of Integrin α 11 Expression and Its Clinical Significance in Gastric Cancer Tissues |
| 投稿时间:2025-03-25 |
| DOI:10.11735/j.issn.1671-170X.2025.10.B006 |
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| 中文关键词: 胃肿瘤 整合素α11 上皮间质转化 侵袭 转移 预后 生物信息学 |
| 英文关键词:gastric neoplasms integrin α 11 epithelial-mesenchymal transition invasion metastasis prognosis bioinformatics |
| 基金项目:河北省医学科学研究课题计划(20250001) |
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| 摘要点击次数: 60 |
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| 中文摘要: |
| 摘 要:[目的] 应用生物信息学方法分析胃癌组织中整合素α11(integrin α 11 ,ITGA11)基因表达及其临床意义,并在临床组织中进行验证。 [方法]采用生物信息学技术筛选与上皮间质转化(epithelial-mesenchymal transition,EMT)相关的差异表达基因。从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中获取胃腺癌(stomach adenocarcinoma,STAD)的RNA-seq表达谱及临床数据,同时从MSigDB中提取EMT相关基因集。通过倍数变化(fold change,FC)结合Wilcoxon检验筛选差异表达基因,并利用R语言survival包进行生存分析。基于STRING数据库构建差异基因的蛋白质互作(protein-protein interaction,PPI)网络,并运用Metascape平台对差异基因进行功能富集分析。采用实时荧光定量PCR技术检测河北省人民医院45例胃癌患者肿瘤组织及癌旁组织中ITGA11、ICAM1和FN1的mRNA表达水平。以实时荧光定量PCR检测结果的ITGA11 mRNA中位值为界值,将45例患者分为高表达组和低表达组,并分析ITGA11 mRNA表达与胃癌临床病理特征的相关性。采用Pearson相关性分析方法,研究ITGA11、ICAM1和FN1三者之间的表达相关性。[结果] 差异基因筛选分析发现,与癌旁组织相比,ITGA11在胃癌组织中的表达水平显著升高(P<0.001)。生存分析结果显示,ITGA11高表达与患者不良预后相关(χ2=6.42,P=0.011)。PPI网络显示,ITGA11、ICAM1、FN1蛋白之间及与其他蛋白具有广泛的相互作用。富集分析显示,ITGA11主要与细胞骨架的调节、焦点黏附、细胞外基质受体相互作用等密切相关。实时荧光定量PCR实验显示,胃癌组织中ITGA11、ICAM1、FN1 mRNA水平(3.14±0.15、3.39±0.31、1.69±0.09)较癌旁组织中(1.01±0.05、1.04±0.06、1.00±0.05)均明显升高(P均<0.001)。ITGA11 mRNA高表达组21例,低表达组24例,低分化、淋巴结转移阳性的肿瘤组织ITGA11 mRNA表达水平更高(P均<0.05)。Pearson相关性分析显示,ITGA11与ICAM1(r=0.672,P<0.01)、ITGA11与FN1(r=0.721,P<0.01)、ICAM1与FN1(r=0.737,P<0.01)表达均呈正相关。[结论] ITGA11在胃癌组织中表达增高,且是胃癌患者预后差的标志物。ITGA11可能通过调控EMT途径参与了肿瘤侵袭转移而促进胃癌进展转移。 |
| 英文摘要: |
| Abstract: [Objective] To analyze the expression of integrin α 11 (ITGA11) and its clinical significance in gastric cancer tissues by bioinformatics methods, and validate it in clinical tissues. [Methods] Bioinformatics methods were applied to screen differentially expressed epithelial-mesenchymal transition (EMT) related genes. RNA-seq expression profiles and clinical data of stomach adenocarcinoma (STAD) were obtained from The Cancer Genome Atlas (TCGA) database, while EMT-related gene sets were extracted from MSigDB. Differentially expressed genes were screened by fold change (FC) combined with the Wilcoxon test, and survival analysis was performed by the R package “survival”. Based on the STRING database, a protein-protein interaction (PPI) network of differentially expressed genes was constructed, and the Metascape platform was utilized to perform functional enrichment analysis on these genes. Real-time quantitative PCR (RT-qPCR) technology was employed to assess the mRNA expression levels of ITGA11, ICAM1, and FN1 in cancer tissues and paracancerous tissues from 45 patients with gastric cancer in Hebei General Hospital. Using the median value of ITGA11 mRNA as the cut-off vaule, 45 patients were divided into a high expression group and a low expression group, and the correlation between ITGA11 mRNA expression and the clinicopathological features of gastric cancer was analyzed. The expression correlation among ITGA11, ICAM1, and FN1 was investigated by Pearson correlation analysis. [Results] Differential gene screening revealed that the expression of ITGA11 in gastric cancer tissues was higher than that in paracancerous tissues (P<0.001), and survival analysis showed that patients with ITGA11 high expression had a poor prognosis (χ2=6.42, P=0.011). The PPI network reveals extensive interactions among ITGA11, ICAM1, and FN1 proteins, as well as with other proteins. Enrichment analysis showed that ITGA11 was closely related to the regulation of action cytoskeleton, focal adhesion and extracellular matrix-interaction. RT-qPCR experiments revealed that the mRNA expression levels of ITGA11, ICAM1, and FN1 in gastric cancer tissues (3.14±0.15, 3.39±0.31, 1.69±0.09) were significantly higher than those in paracancerous tissues (1.01±0.05, 1.04±0.06, 1.00±0.05) (all P<0.001). There were 21 cases in the high ITGA11 mRNA expression group and 24 cases in the low expression group, the expression level of ITGA11 mRNA was higher in poorly differentiated and lymph node metastasis-positive cancer tissues (all P<0.05). Pearson correlation analysis revealed a positive correlation between ITGA11 and ICAM1 (r=0.672, P<0.01), ITGA11 and FN1 (r=0.721, P<0.01), as well as between ICAM1 and FN1 (r=0.737, P<0.01). [Conclusion] ITGA11 is overexpression in gastric cancer tissues and may serve as a biomarker for poor prognosis in patients. It potentially promotes the progression and metastasis of gastric cancer by regulating the EMT pathway, which plays a critical role in tumor invasion and metastasis. |
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