乳腺癌免疫相关预后分子标志物的鉴定

Identification of immune-related prognostic molecular markers of breast cancer

目的探讨S100钙结合蛋白P(S100 calciumbinding protein P,S100P)和胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP)在乳腺癌患者中的表达特征及其与预后的关系。方法利用GEPIA数据库和bc-GenExMiner v4.3分析S100P和TSLP在乳腺癌组织中的表达水平,使用Kaplan-Meier Plotter分析S100P和TSLP对乳腺癌患者预后的影响,利用STRING数据库对S100P和TSLP进行蛋白相互作用网络分析。利用Linked Omics数据库分析S100P和TSLP各自的共表达基因,并采用基因本体(gene ontology,GO)及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析评估S100P和TSLP的共表达基因在相关生物学过程和信号通路中的作用。通过TIMER分析S100P和TSLP与乳腺癌免疫浸润的相关性。结果乳腺癌患者的S100P表达显著高于正常人群,TSLP表达显著低于正常人群(P<0.05)。S100P高表达患者的总生存期、无病生存期和远处无转移生存期均显著短于S100P低表达患者(P<0.05);TSLP高表达患者的远处无转移生存期显著长于TSLP低表达患者(P<0.05)。蛋白质相互作用表明,S100P与白细胞介素-11表现出较强的互作关系,TSLP与白细胞介素家族相互作用较强,S100P和TSLP的共表达基因主要负责DNA复制和免疫功能等生物学功能。TSLP与乳腺癌免疫细胞浸润具有相关性。结论S100P和TSLP可作为预测乳腺癌预后的生物标志物,TSLP有助于评估乳腺癌患者肿瘤免疫浸润情况,为乳腺癌患者预测预后和肿瘤免疫治疗提供理论依据。

Objective To investigate the expression characteristics of S100 calcium binding protein P(S100P)and thymic stromal lymphopoietin(TSLP)in patients with breast cancer and their relationship with prognosis.Methods GEPIA database and bc-GenExMiner v4.3 were used to analyze the expression levels of S100P and TSLP in breast cancer tissues,and Kaplan-Meier Plotter was used to analyze effects of S100P and TSLP on patient prognosis.The protein interaction network analysis of S100P and TSLP were carried out by using STRING database.The co-expressed genes of S100P and TSLP were analyzed using Linked Omics database,and the role of S100P and TSLP co-expressed genes in related biological processes and signaling pathways were evaluated by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The correlation between S100P and TSLP and breast cancer immunoinfiltration was analyzed by TIMER.Results The expression of S100P in breast cancer patients was significantly higher than that in normal population,and the expression of TSLP was significantly lower than that in normal population(P<0.05).The overall survival,disease-free survival and distant metastasis-free survival of patients with high S100P expression were significantly shorter than those of patients with low S100P expression(P<0.05).The distant metastasis-free survival of patients with high expression of TSLP was significantly longer than that of patients with low expression of TSLP(P<0.05).The results of protein interaction showed that S100P had a strong interaction with interleukin-11,and TSLP had a strong interaction with interleukin family proteins.The co-expressed genes of S100P and TSLP were mainly responsible for biological functions such as DNA replication and immune function.TSLP was correlated with breast cancer immune cell infiltration.Conclusion S100P and TSLP can be used as biomarkers to predict the prognosis of breast cancer,and they can also help to evaluate the tumor immunoinfiltration in breast cancer patients,and TSLP could provide theoretical basis for predicting the prognosis and tumor immunotherapy in breast cancer patients.