LDHA及LDHB对胃癌组织中免疫微环境的影响及临床意义

Influence of LDHA and LDHB on immune microenvironment in gastric cancer and its clinical implications

目的探讨LDHA及LDHB在胃癌组织中的表达、预后意义及对免疫微环境的影响。方法从HPA和TCGA数据库中筛选出375例胃癌患者的免疫组化染色图片、临床信息和转录组数据,分析LDHA及LDHB表达与胃癌临床病理特征的关系。采用Kaplan-Meier法和Cox回归分析探究LDHA及LDHB表达与胃癌患者总生存期(overall survival,OS)及无瘤生存期(disease-free survival,DFS)的关系;采用生物信息学ssGSEA算法分析LDHA及LDHB对胃癌组织中免疫微环境的影响。结果与癌旁正常组织相比,胃癌组织中LDHA及LDHB的mRNA及蛋白均明显上调(P均<0.05)。LDHA高表达胃癌患者比低表达患者具有更短的OS,LDHB高表达胃癌患者比低表达患者具有更短的DFS(HR=1.36、1.65,P均<0.05)。多因素Cox回归分析显示,LDHA及LDHB的表达可影响包括Th2细胞、NK细胞在内的多种免疫细胞的含量(P均<0.05)。LDHA及LDHB均是胃癌患者预后的独立影响因素(HR=1.31、1.55,P均<0.05)。结论LDHA及LDHB在胃癌组织中高表达,提示患者预后较差,并对胃癌组织中免疫微环境造成一定程度的影响。

Purpose To investigate the expression of lactate dehydrogenase(LDH)subtypes in gastric cancer tissues,prognostic significance and effects on immune microenvironment.Methods Immunohistochemical staining sections,clinical information and transcriptome data of 375 patients with gastric cancer from HPA and TCGA databases were used to analyze the relationship between the expression of LDH subtypes and clinicopathological features.Kaplan-Meier analysis and Cox regression analysis were used to explore the relationship between expression of subtypes and overall survival(OS)and disease-free survival(DFS),and ssGSEA algorithm was used to explore the effect of each subtype on immune microenvironment in gastric cancer tissues.Results Compared with normal tissues,mRNA and protein expression of different subtypes were significantly higher in gastric cancer tissues(P<0.05).In addition,patients with high expression of LDHA had a shorter OS compared with patients with low expression of LDHB,and patients with high expression of LDHB had a shorter DFS compared with patients with low expression of LDHB(HR=1.36,1.65,all P<0.05).Multivariate Cox regression analysis showed that LDHA and LDHB were independent prognostic factors(HR=1.31,1.55,all P<0.05).Finally,the expression of different subtypes affected the content of immune cells including Th2 cells,NK cells,etc(all P<0.05).Conclusion Lactate dehydrogenase subtypes are highly expressed in gastric cancer tissues,suggesting a poor prognosis of patients,and also affect the immune microenvironment in tissues to a certain extent.