双原发恶性肿瘤的胃癌患者肿瘤细胞差异表达基因分析OA
Analysis of differentially expressed genes in gastric cancer patients with double primary malignant tumors
目的 筛选并分析双原发性恶性肿瘤的胃癌患者肿瘤细胞中的差异表达基因,以探索胃癌患者发生双原发恶性肿瘤可能的分子机制.方法 选取2023年6月-2024年12月收治的胃癌患者80例,其中单原发恶性肿瘤患者、双原发恶性肿瘤患者(患有其他部位的原发恶性肿瘤且与胃癌无关)各40例.将术中留取的肿瘤组织制作单细胞悬液,构建单细胞测序文库并进行高通量测序.鉴定出肿瘤细胞后,比较两类患者肿瘤细胞的基因表达谱,使用MAST算法筛选差异表达基因.对筛选出的差异表达基因进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析.结果 在两类患者的肿瘤细胞中,共筛选出1 865个差异表达基因,双原发恶性肿瘤患者表达上调基因1 023个(如表皮生长因子受体基因等)、表达下调基因842个(如磷酸酶及张力蛋白同源基因等).GO富集分析结果显示,差异表达基因显著富集于细胞增殖、迁移、免疫反应调控等生物过程,蛋白激酶活性调节、转录因子结合等生物功能,并与细胞外基质成分、细胞膜受体复合物等细胞组成成分相关.KEGG富集分析结果显示,差异表达基因显著富集于 PI3K-AKT信号通路、MAPK信号通路、Wnt信号通路和PD-1/PD-L1信号通路,4条信号通路的多个相关基因在双原发恶性肿瘤患者中表达上调(如PIK3CA、AKT1、MAPK1、MAPK3、CTNNB1、PD-L1等).结论 双原发性恶性肿瘤的胃癌患者肿瘤细胞中存在多种差异表达基因.这些差异表达基因与细胞增殖迁移调节、免疫反应调节、细胞信号转导等关键生物过程有关;同时涉及多种细胞信号通路异常激活,如PI3K-AKT、MAPK、Wnt信号通路等.
Objective To screen and analyze the differentially expressed genes(DEGs)in tumor cells of gastric cancer patients with double primary malignant tumors,in order to explore the possible molecular mechanisms of double pri-mary malignant tumors in patients with gastric cancer.Methods Eighty gastric cancer patients admitted from June 2023 to December 2024 were selected,including 40 patients with single primary malignant tumor and 40 patients with double prima-ry malignant tumors(with primary malignant tumors at other unrelated sites).Single-cell suspensions were prepared from tumor tissues collected during surgery,and single-cell sequencing libraries were constructed for high-throughput sequencing.After identifying tumor cells,the gene expression profiles of tumor cells between the two groups were compared,and DEGs were screened using the MAST algorithm.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed on the screened DEGs.Results A total of 1,865 DEGs were identified between the two groups.Among them,1,023 genes were up-regulated(e.g.,EGFR)and 842 genes were down-regulated(e.g.,PTEN)in patients with double primary malignant tumors.GO enrichment analy-sis showed that DEGs were significantly enriched in biological processes such as cell proliferation,migration,and regulation of immune response;in biological functions including regulation of protein kinase activity and transcription factor binding;and in cellular components such as extracellular matrix components and cell membrane receptor complexes.KEGG enrich-ment analysis revealed that DEGs were significantly enriched in the PI3K-AKT signaling pathway,MAPK signaling path-way,Wnt signaling pathway,and PD-1/PD-L1 signaling pathway.Multiple related genes in these four pathways were up-regulated in patients with double primary malignant tumors(e.g.,PIK3CA,AKT1,MAPK1,MAPK3,CTNNB1,PD-L1).Conclusions Multiple DEGs exist in tumor cells of gastric cancer patients with double primary malignant tumors.These DEGs are mainly enriched in key biological processes such as regulation of cell proliferation and migration,regulation of immune response,and cellular signal transduction.Several cellular signaling pathways(e.g.,PI3K-AKT,MAPK,Wnt signaling pathways)are abnormally activated in double primary malignant tumors.
周杨;张璐璐;朱元增
河南省人民医院 郑州大学人民医院 河南大学人民医院胃肠外科,河南郑州 450000河南省人民医院 郑州大学人民医院 河南大学人民医院胃肠外科,河南郑州 450000河南省人民医院 郑州大学人民医院 河南大学人民医院胃肠外科,河南郑州 450000||新疆生产建设兵团第十三师红星医院肝胆胃肠外科,新疆哈密 839000
医药卫生
胃癌双原发恶性肿瘤单细胞测序
gastric carcinomadouble primary malignant neoplasmssingle-cell RNA sequencing
《山东医药》 2026 (3)
6-9,14,5
河南省医学科技攻关项目(LHGJ20230077).
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