Objective: To explore the expression characteristics of ELK3 and its role in the occurrence, progression and prognosis of gastric cancer.
Methods: We analyzed the expression characteristics of ELK3 in gastric cancer based on E-MTAB-6693 dataset and explored the prognostic value of ELK3 using Kaplan-Meier survival analysis and univariate and multivariate Cox regression analysis. Chip-Atlas, ChipBase, Genes Transcription Regulation Database, and hTFtarget were used for predicting the target genes of ELK3 and constructing the transcription regulation network. Functional enrichment analysis of the target genes was performed using R software. The proportions of infiltrating immune cells in gastric cancer were analyzed using Cibersort tool, and the Pearson coefficients between ELK3 and these cells were calculated. The expression profile of ELK3 was verified based on Gene Expression Profiling Interactive Analysis and Human Protein Atlas databases. We also collected 5 pairs of gastric cancer and adjacent tissue samples and detected the expression of ELK3 at both the mRNA and protein levels using RT-PCR and Western blotting.
Results: In public datasets and clinical samples, ELK3 was highly expressed in gastric cancer (P < 0.05), and its expression increased with the progression of M stage, AJCC stage, and perineural invasion (P < 0.05). ELK3 expression was correlated with N stage, AJCC stage, Lauren classification, differentiation, pathological classification, and microsatellite status of gastric cancer (P < 0.05). A high expression of ELK3 was associated with significantly reduced overall survival and disease-free survival of the patients, and served as an independent prognostic factor of gastric cancer (P < 0.05). Comprehensive analysis identified 176 potential target genes of ELK3, and enrichment analysis showed that ELK3 may regulate Rap1, AMPK, chemokines, VEGF, TNF, and tumor PD-L1/PD-1 signaling (PP < 0.05). The expression of ELK3 was negatively correlated with regulatory T cells, follicular helper T cells, and CD8+T cells in gastric cancer (P < 0.05).
Conclusion: ELK3 acts as an oncogene in gastric cancer, and its high expression may promote the occurrence, progression and immune escape of gastric cancer.
目的: 探讨ELK3在胃癌中的表达特征和潜在功能。
方法: 采用非配对t检验、χ2检验分析E-MTAB-6693数据集ELK3在胃癌的表达特征；Kaplan-Meier生存分析、单因素和多因素Cox回归分析ELK3对预后的预测能力。Chip-Atlas、ChipBase、基因转录调控数据库、hTFtarget预测并构建ELK3转录调控网络。R软件“org.Hs.eg.db”包对靶基因进行功能富集分析。Cibersort工具分析胃癌组织中浸润性免疫细胞的比例，并计算Pearson系数分析ELK3与这些细胞的相关性。使用基因表达谱分析人类蛋白图谱公共数据库验证ELK3的表达。收集5组胃癌临床样本，利用rt-PCR验证ELK3的mRNA水平表达，利用Western blot验证ELK3在配对胃癌组织中蛋白水平表达差异。
结果: 在公共数据集和临床样本中ELK3在胃癌中高表达（P < 0.05）；其表达随M分期、AJCC分期、神经侵袭的进展而升高（P < 0.05）。χ2检验表明ELK3表达水平与N分期、AJCC分期、Lauren分型、分化程度、病理分型、微卫星状态相关（P < 0.05）。ELK3高表达患者的总体生存期和无病生存期较低表达患者显著降低，是胃癌的独立预后因素（P < 0.05）。综合鉴定出176个潜在的ELK3转录调控靶基因，富集分析表明ELK3可能调控Rap1、AMPK、趋化因子、VEGF、TNF、肿瘤PD-L1/PD-1信号（P < 0.05）。ELK3表达与胃癌中调节T细胞、滤泡辅助性T细胞、CD8+T细胞数量呈负相关（P < 0.05）。
结论: ELK3在胃癌中充当癌基因，可能促进胃癌细胞发生、发展和免疫逃避。
Keywords: ELK3; gastric cancer; immune escape; prognosis; transcriptional regulation.