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探究COX-2在胃癌中的表达模式及其与胃癌患者临床病理特征的相关性分析
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Abstract:
目的：深度探讨环氧化酶-2 (Cyclooxygenase-2,COX-2, PTGS2)在胃癌中的表达模式及其与胃癌患者临床病理特征的相关性。方法：首先，应用免疫组织化学法，检测2003~2013年及2020~2022年大理大学第一附属医院胃癌患者标本各25例作为研究对象，并对COX-2蛋白的表达与胃癌患者临床病理特征进行相关性分析。其次，利用TCGA在线数据库挖掘COX-2 mRNA在泛癌中的表达及差异，借助STRING在线数据库构建COX-2相关上下游基因的蛋白互作(PPI)网络，并对这些基因进行GO功能注释和KEGG通路富集分析。最后，通过基因富集分析(GSEA)探索COX-2可能导致胃癌的关键信号通路。结果：在50例免疫组化切片中，高表达占50% (25/50)、低表达占46% (23/50)、不表达占4% (2/50)，COX-2主要在胃癌和癌旁的细胞浆中表达。COX-2的表达与患者的临床病理特征不相关(P > 0.05)。GO富集分析表明，靶点主要富集在不饱和脂肪酸代谢过程(Unsaturated Fatty Acid Metabolic Process)、分泌颗粒腔(Secretory Granule Lumen)和铁离子结合(Iron Ion Binding)等生物学过程。KEGG富集结果表明，靶点主要富集于花生四烯酸代谢(Arachidonic Acid Metabolism)、血清素能突触(Serotonergic Synapse)和脂质与动脉粥样硬化(Lipid and Atherosclerosis)等。GESA富集结果发现，COX-2通过JAK-STAT通路、IL-17通路等导致胃癌的发生。结论：COX-2在胃癌的细胞浆中表达，且与胃癌患者的临床病理特征不相关，可通过多种途径导致胃癌的发生。这一发现打破了人们一直以来认为的COX-2导致胃癌的发生且与患者的临床特征密切相关的思维，为治疗胃癌患者提供了新的思路。
Objective: To deeply investigate the expression pattern of cyclooxygenase-2 (COX-2, PTGS2) in gastric cancer and its correlation with patient clinicopathological characteristics. Methods: Firstly, immunohistochemistry was applied to detect COX-2 protein expression in gastric cancer specimens from a total of 50 patients, with 25 cases from each of the two periods: 2003~2013 and 2020~2022 at the First Affiliated Hospital of Dali University, followed by correlation analysis between COX-2 protein expression and the clinicopathological characteristics of the patients. Secondly, the TCGA online database was utilized to explore COX-2 mRNA expression and differences across pan-cancer analyses. The STRING online database was employed to identify upstream and downstream genes related to COX-2 in gastric cancer for protein-protein interaction (PPI) analysis, and these genes were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, Gene Set Enrichment Analysis (GSEA) was conducted to explore key signaling pathways through which COX-2 may contribute to gastric cancer. Results: Among the 50 immunohistochemical slides, high expression was observed in 50% (25/50), low expression in 46% (23/50), and no expression in 4% (2/50). COX-2 was primarily expressed in the cytoplasm of both gastric cancer cells and adjacent non-cancerous mucosal tissues. No significant correlation was found between COX-2 expression and the clinicopathological characteristics of the patients (P > 0.05). GO enrichment analysis indicated that the target genes were mainly enriched in
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