S100P在NSCLC中的表达、信号通路和预后关系生物信息分析及验证

Bioinformatics analysis and validation of S100P expression,signaling pathway and prognosis in NSCLC

目的探讨S100P在非小细胞肺癌(NSCLC)中的表达、信号通路和预后关系。方法采用生物信息分析方法比对TCGA数据库中S100P基因在NSCLC患者组织中的表达情况。构建S100P蛋白-蛋白相互作用网络,探讨其相关信号通路。根据S100P基因在NSCLC患者癌组织中表达的中位数,分为高表达组和低表达组。Log-rank检验分析S100P表达与NSCLC患者预后的关系。同时回顾性分析四川省资阳市人民医院肿瘤科收治的48例NSCLC患者资料,采用免疫组织化学检测NSCLC患者癌组织和癌旁正常组织中S100P蛋白表达水平与NSCLC患者临床病理特征的关系。结果 S100P蛋白在肺腺癌组织中S100P基因表达水平显著高于癌旁组织(P<0.05),且不同临床分期表达水平存在差异(F=3.74,P<0.05)。与S100P蛋白相互作用较为紧密的蛋白网络节点数50个,区域聚类指数为0.39,蛋白相互作用网络富集显著(P<0.05)。与S100P基因正相关表达最显著的基因为FURIN基因(r=0.55,P<0.05),与S100P基因负相关表达最显著的基因为CAMK1(r=-0.38,P<0.05)。S100P高表达组无疾病进展生存显著低于低表达组(HR=1.3,P<0.05)。免疫组织化学检测显示S100P蛋白在癌组织中的阳性表达与NSCLC患者的临床分期和纵隔淋巴结转移有关(P值均<0.05),而与患者年龄、性别、肿瘤大小、病理类型、病例分级和有无胸水无关(P值均>0.05)。结论 S100P基因在NSCLC患者肿瘤组织中呈现高表达,并与NSCLC患者预后不良有关。

Objective To investigate the expression of S100P in non-small cell lung cancer(NSCLC),the relationship between signal pathway and prognosis.Methods Firstly,the expression of S100P gene in NSCLC patients was compared by bioinformatics.Then,S100P protein protein interaction network was constructed to explore its related signaling pathway.According to the median expression of S100P gene in cancer tissues of NSCLC patients,it was divided into high expression group and low expression group.Log rank test was used to analyze the relationship between S100P expression and the prognosis of NSCLC patients.48 NSCLC patients admitted to Ziyang People′s Hospital of Sichuan Province were retrospectively analyzed.The relationship between the expression of S100P protein in the cancer tissues and adjacent normal tissues of NSCLC patients and the clinicopathological characteristics of NSCLC patients was detected by immunohistochemistry.Results The expression level of S100P gene in lung adenocarcinoma was significantly higher than that in paracancerous tissues(P<0.05),and there was a difference in the expression level of S100P gene in different clinical stages(F=3.74,P<0.05).There were 50 protein network nodes with close interaction with S100P protein,the regional clustering index was 0.39,and the protein interaction network was significantly enriched(P<0.05).The most significant genes with positive correlation with S100P gene were FURIN gene,correlation coefficient r=0.55(P<0.05);CAMK1,correlation coefficient r=-0.38(P<0.05),was the most significant gene negatively correlated with S100P gene;the disease-free progression survival of S100P high expression group was significantly lower than that of low expression group(HR=1.3,P<0.05).Immunohistochemistry showed that S100P protein expression in cancer tissue was related to clinical stage and mediastinal lymph node metastasis(all P<0.05),but not to age and gender,tumor size,pathological type,case classification,and presence or absence of pleural fluid(all P>0.05).Conclusions S100P gene is highly expressed in NSCLC patients,which is related to the poorprognosis of NSCLC patients.