胃腺癌患者LHPP表达及其对癌细胞生物学功能的影响  

Expression of LHPP in patients with gastric adenocarcinoma and its effect on biological function of carcinoma cells

作　　者：向敏 舒扬[2] 盛玉程 武晓白 郭若楠 蒋一凡 XIANG Min;SHU Yang;SHENG Yucheng;WU Xiaobai;GUO Ruonan;JIANG Yifan(Department of Clinical Laboratory,the Affiliated Hospital of Jiangsu University,Zhenjiang 212001,Jiangsu,China;Department of Central Laboratory,the Affiliated Hospital of Jiangsu University,Zhenjiang 212001,Jiangsu,China)

机构地区：[1]江苏大学附属医院检验科,江苏镇江212001 [2]江苏大学附属医院中心实验室,江苏镇江212001

出　　处：《检验医学》2025年第1期41-48,共8页Laboratory Medicine

基　　金：镇江市社会发展指导性科技计划(FZ2023055);镇江市社会发展重点研发计划(SH2023003)。

摘　　要：目的探讨胃腺癌患者磷酸赖氨酸磷酸组氨酸无机焦磷酸盐磷酸酶(LHPP)表达的变化,及其对癌细胞生物学功能的影响。方法选取2020年10月—2021年6月江苏大学附属医院胃腺癌患者21例,收集其癌组织和癌旁组织。通过生物数据库分析LHPP在胃癌中的表达及其与患者预后的关系。检测胃腺癌患者癌组织和正常胃组织,以及不同细胞株(人胃黏膜上皮细胞株GES-1和胃癌细胞株HGC-27、AGS、MKN-45、SGC-7901、MGC-803)中LHPP蛋白和mRNA的表达情况。构建胃癌细胞干扰模型,并采用细胞生物学实验评估LHPP对胃癌细胞增殖和迁移能力的影响。采用基因本体(GO)富集和京都基因与基因组数据库(KEGG)信号通路分析评估LHPP相关基因的作用。结果癌症基因组图谱计划(TCGA)数据库、综合基因表达(GEO)数据库和人类蛋白质图谱(HPA)数据库的分析结果显示,胃癌组织LHPPmRNA和蛋白表达均低于癌旁组织(P<0.05);Kaplan-Meier Plotter数据库的分析结果显示,LHPP高表达的胃癌患者总生存期、首次进展生存期和再次进展生存期均长于LHPP低表达的胃癌患者[风险比(HR)分别为0.66、0.57、0.64,95%可信区间(CI)分别为0.54~0.81、0.45~0.73、0.48~0.85]。各胃癌细胞LHPP蛋白和mRNA相对表达量与GES-1细胞比较,差异均有统计学意义(P<0.05),选择AGS细胞进行后续实验。胃腺癌患者癌组织中LHPP蛋白和mRNA相对表达量均低于癌旁组织(P<0.05)。LHPP可抑制AGS细胞的增殖和迁移。LHPP在胃癌中的主要功能为有丝分裂中的细胞周期调控、正向调控DNA代谢过程、蛋白折叠、调控核质转运等,主要涉及细胞周期、TPX2调控AURKA激活和表观遗传学调控基因表达等信号通路。结论胃腺癌患者LHPP呈低表达,且与患者预后密切相关。LHPP对胃腺癌细胞的增殖和迁移有抑制作用。Objective To investigate the role of phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)expression in patients with gastric adenocarcinoma and its effect on the biological function of carcinoma cells.Methods A total of 21 patients with gastric adenocarcinoma from the Affiliated Hospital of Jiangsu University from October 2020 to June 2021 were enrolled to collect gastric cancer tissues and adjacent tissues.The expression of LHPP in gastric cancer and its relationship with prognosis were analyzed by biological database.The expression of LHPP protein and mRNA in cancer tissues and adjacent tissues of patients with gastric cancer and different cell lines(human gastric mucosal epithelial cell line GES-1 and gastric cancer cell line HGC-27,AGS,MKN-45,SGC-7901,MGC-803)were determined.A gastric cancer cell interference model was constructed,and the effects of LHPP on the proliferation and migration of gastric cancer cells were evaluated by cell biology experiments.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis were used to evaluate the role of LHPP related genes.Results The analysis results of the Cancer Genome Atlas(TCGA),the Gene Expression Omnibus(GEO)and the Human Protein Atlas(HPA)databases showed that the LHPP mRNA and protein expressions in gastric cancer tissues were lower than those in adjacent tissues(P<0.05).The analysis results of Kaplan-Meier Plotter database showed that the overall survival,first progression survival and reprogression survival of gastric cancer patients with high LHPP expression were longer than those with low LHPP expression[hazard ratios(HR)were 0.66,0.57 and 0.64,95%confidence intervals(CI)were 0.54-0.81,0.45-0.73 and 0.48-0.85,respectively].The relative expression levels of LHPP protein and mRNA in all gastric cancer cell lines were statistically significant compared with GES-1 cells(P<0.05),and AGS cells were selected for follow-up tests.The relative expression levels of LHPP protein and mRNA in gastric canc

关 键 词：磷酸赖氨酸磷酸组氨酸无机焦磷酸盐磷酸酶 胃腺癌 增殖 迁移 预后 

分 类 号：Q555[生物学—生物化学]