胃癌中LAMP5表达及预后意义分析

The expression and prognostic significance of LAMP5 in gastric cancer

目的:探究溶酶体相关膜蛋白5(LAMP5)在胃癌中的表达及预后意义。方法:选择胃癌组织130例及其邻近正常胃组织标本40例,采用组织芯片免疫组化检测LAMP5蛋白表达,分析LAMP5表达与患者临床病理特征及预后的关系。通过TCGA数据库验证胃癌与正常胃组织中LAMP5表达差异,LAMP5表达与患者临床病理特征及总体生存期(overall survival,OS)的关系。采用基因富集分析(gene set enrichment analysis,GSEA)研究LAMP5可能的作用机制。结果:组织芯片免疫组化表明,与正常胃组织相比,胃癌组织LAMP5表达增高,LAMP5表达与胃癌分期(P=0.045)、肿瘤大小(P=0.006)相关。Kaplan-Meier生存曲线分析表明,LAMP5表达与胃癌患者OS呈负相关(P=0.035)。TCGA数据分析显示,与正常胃组织相比,胃癌组织中LAMP5表达增高(P=0.016);Kruskal检验表明LAMP5表达与肿瘤分级G3/G1(P=0.024)及G3/G2(P<0.001),分期SⅡ/Ⅰ(P<0.001)、SⅢ/Ⅰ(P<0.001)及SⅣ/Ⅰ(P<0.001),肿瘤大小T2/T1(P=0.002)、T3/T1(P<0.001)、T4/T1(P<0.001)、T3/T2(P=0.026)及T4/T2(P=0.005)相关。Kaplan-Meier生存曲线分析显示LAMP5表达越高,胃癌患者OS越短(P=0.007)。单因素COX回归分析表明,年龄(P=0.006)、分期(P<0.001)、肿瘤大小(P=0.032)、淋巴结转移(P=0.006)、远处转移(P=0.024)和LAMP5表达(P=0.004)可作为胃癌患者的预后指标;多因素COX回归分析表明,年龄(P<0.001)、性别(P=0.047)和LAMP5表达(P<0.001)可作为胃癌患者预后的独立指标。Gene Ontology(GO)富集分析显示,LAMP5可能参与促进胶原结合、细胞外基质结构成分、糖胺聚糖结合、生长因子结合、整合素结合等通路,抑制呼吸作用、线粒体呼吸链复合物组件、呼吸电子传输链、NADH脱氢酶复合物组件、核糖体结构成分等通路。Kyoto Encyclopedia of Genes and Genomes(KEGG)富集分析表明,LAMP5可能促进ECM受体相互作用、焦点粘附、TGF-β信号通路、Hedgehog信号通路、癌症途径等通路,抑制阿尔茨海默病、氧化磷酸化、亨廷顿病、帕金森病、核糖体等通路。结论:LAMP5在胃癌组织中高表达,LAMP5表达越高,患者总体生存期越差,LAMP5可作为胃癌患者预后的独立影响因素。

Objective:To investigate the expression and prognostic significance of lysosome-associated membrane protein 5(LAMP5)in gastric carcinoma(GC).Methods:The protein expression of LAMP5 in 130 GC and 40 normal stomach tissues was detected by tissue chip immunohistochemistry method.The expression of LAMP5 in GC and normal stomach tissues,and the relationship between LAMP5 and clinicopathological features and prognosis of GC patients were analyzed.Subsequently,TCGA database was used to further verify the different expression of LAMP5 in GC and normal tissues,and the relationship between the expression of LAMP5 and the clinicopathological features and overall survival(OS)of patients.Gene set enrichment analysis(GSEA)illustrated the possible pathways of LAMP5.Results:Immunohistochemical analysis of tissue chips clarified compared with normal stomach tissues,the expression of LAMP5 was correlated with stage(S)and tumor size(T),but not with age,sex,grade(G),lymph node metastasis(N)or distant metastasis(M).Kaplan-Meier(K-M)analysis elucidated LAMP5 expression was negatively correlated with the OS of GC patients.TCGA analysis revealed compared with normal gastric tissues,the expression of LAMP5 was higher in GC tissues.Kruskal test revealed LAMP5 expression was correlated with G,S and T.K-M analysis displayed the expression of LAMP5 was negatively correlated with the prognosis of GC patients.Univariate COX analysis displayed age,stage,T,N,M and LAMP5 were prognostic indicators.Multivariate COX analysis showed age,sex and LAMP5 could be independent prognostic indicators.Subsequently,Gene Ontology(GO)enrichment analysis illuminated LAMP5 involved in promoting collagen binding,extracellular matrix structural components,glycosaminoglycan binding,growth factor binding,integrin binding and other pathways;and inhibiting of respiration,mitochondrial respiratory chain complex components,respiratory electron transport chain,NADH dehydrogenase complex components,ribosome structural components and other pathways.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment illuminated LAMP5 may be involved in promoting ECM receptor interaction,focal adhesion,TGF-βpathway,HEDGEHOG pathway,cancer pathway,etc;and inhibiting Alzheimer’s disease,oxidative phosphorylation,Huntington’s disease,Parkinson’s disease,ribosome and other pathways.Conclusion:LAMP5 was highly expressed in GC tissues and negatively correlated with the overall survival of GC patients.LAMP5 could be regarded as an independent prognostic factor for GC patients.