泛癌组织STIP1的表达与肿瘤免疫浸润及预后相关:基于生物信息学方法

STIP1 correlates with tumor immune infiltration and prognosis as a potential immunotherapy target:a pan-cancer bioinformatics analysis

目的本研究旨在对压力诱导磷酸蛋白1(STIP1)进行泛癌分析,探讨其表达水平与肿瘤预后的关系及其在免疫学中的作用。方法使用生物信息学方法分析TCGA、TARGET和GTEx数据库,研究STIP1在各种类型肿瘤组织中的表达及预后价值;采用免疫组化检测STIP1在10例配对结直肠癌组织以及正常组织中的表达情况;STIP1与肿瘤突变负荷(TMB)、微卫星不稳定(MSI)的关系进一步被揭示;使用MCPcounter、TIMER分析STIP1的表达与免疫细胞的浸润情况;分析STIP1与免疫调节因子的相关性;根据各肿瘤中STIP1的最优截断值,将样本分为高低表达组;使用蛋白互作网络分析鉴定与STIP1相关的蛋白;通过功能富集分析寻找STIP1可能参与的调节通路。结果与正常组织相比,STIP1在大多数肿瘤中高表达(P<0.05),以及免疫组化的结果显示其在结直肠癌组织中高表达。STIP1的表达水平与多种类型肿瘤的临床分期相关(P<0.05)。在部分肿瘤中,STIP1的表达上调与肿瘤患者的不良预后(总体生存期、疾病特异性生存期、无病生存期和无进展生存期)显著相关(P<0.05)。STIP1表达与多种肿瘤的肿瘤突变负荷、微卫星不稳定、免疫浸润以及免疫调节相关因子显著相关(P<0.05)。蛋白互作网络分析提示STIP1相关的蛋白有热休克蛋白A家族成员4、热休克蛋白A家族成员8、热休克蛋白90α家族A类成员1等。KEGG富集分析提示在肝癌组织中STIP1高表达可能与戊酸盐代谢、色氨酸代谢、丁酸盐代谢等通路有关;HALLMARK富集分析提示在肝癌组织中STIP1高表达可能与胆汁酸代谢、脂肪酸代谢等有关。结论STIP1在多数肿瘤中表达上调,STIP1与部分肿瘤的临床分期、不良预后、肿瘤突变负荷、微卫星不稳定、免疫细胞浸润以及免疫调节因子相关。

Objective To investigate the correlation of stress-inducible phosphoprotein 1(STIP1)expression level with prognosis of different cancers and its potential role in immunotherapy.Methods TCGA,TARGET and GTEx databases were used for bioinformatic analysis of STIP1 expression level and its prognostic value in different cancers.We also detected STIP1 expression immunohistochemically in 10 pairs of colorectal cancer and adjacent tissues.We further analyzed the correlation of STIP1 expression level with tumor mutational burden,microsatellite instability,immune cell infiltration,immune regulators and outcomes of different cancers.STIP1-related proteins were identified using protein-protein interaction(PPI)network analysis,and functional enrichment analysis was performed to analyze the regulatory pathways involving STIP1.Results Bioinformatics analysis showed that STIP1 was highly expressed in most tumors compared with the normal tissues(P<0.05),which was confirmed by immunohistochemistry of the 10 pairs of colorectal cancer tissues.STIP1 expression level was correlated with clinical stages of multiple cancers(P<0.05),and in some cancer types,an upregulated STIP1 expression was correlated with a poor prognosis of the patients in terms of overall survival,disease-specific survival,disease-free survival and progression-free survival(P<0.05).STIP1 expression was significantly correlated with tumor mutational burden,microsatellite instability,immune cell infiltration and immunomodulatory factors in most tumors(P<0.05).PPI network analysis indicated that STIP1-related proteins included HSPA4,HSPA8,and HSP90AA1.KEGG enrichment analysis suggested that the high expression of STIP1 in liver cancer was related mainly with valerate metabolism,tryptophan metabolism,and butyrate metabolism pathways;HALLMARK enrichment analysis suggested high STIP1 expression in liver cancer was involved in bile acid and fatty acid metabolism.Conclusion STIP1 is up-regulated in multiple cancer types and its expression level is correlated with clinical tumor stage,tumor mutational burden,microsatellite instability,immune cell infiltration and immunomodulatory factors.