摘要
目的本研究旨在探究分泌型磷酸蛋白2(SPP2)在肝细胞癌预后中的预测价值和参与免疫调控的潜在机制。方法探究SPP2在肝细胞癌预后中的预测价值的方法:从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)分别获得了肝细胞癌的RNA-Seq表达数据和临床相关资料。此外,收集2015~2018年间在青海大学附属医院行手术切除治疗的21例肝细胞癌组织和癌旁组织标本进行IHC、Western Blot检测,分析SPP2在肝细胞癌中的表达情况。基于Kaplan-Merier生存分析法、单因素和多因素COX逻辑回归法分析SPP2表达与肝细胞癌患者预后的关系;探究SPP2参与免疫调控的潜在机制的方法:基于TIMER数据库和单样本基因集富集分析(ssGSEA)法评估SPP2与免疫细胞浸润的关系。结果来自TCGA和GEO队列的RNA-Seq数据显示,SPP2在肝细胞癌组织中的表达显著低于癌旁组织,且SPP2高表达的患者有更好的临床预后;单因素和多因素COX回归的分析结果表明,SPP2可以独立于其他临床因素,作为肝细胞癌的独立预后因子;IHC和Western Blot显示,SPP2在肝细胞癌组织中的表达低于癌旁组织,且在高病理分期中的表达更低,与SPP2高表达的患者相比,低表达SPP2的患者总体生存时间更短;免疫浸润分析显示,SPP2表达与肿瘤相关巨噬细胞及Th2细胞的浸润程度具有显著的负相关性。结论SPP2可作为肝细胞癌的潜在不良预后预测生物标志物,并有望成为监测肝细胞癌进展的特异生物标志物和潜在的治疗靶点;SPP2的表达水平与免疫细胞的浸润程度相关。
Objective The present study intended to explore the predictive value of secreted phosphoprotein 2(SPP2)in the prognosis of hepatocellular carcinoma(HCC)and the potential mechanisms involved in immune regulation.Methods Approaches to explore the predictive value of SPP2 in the prognosis of hepatocellular carcinoma:Data of RNA-Seq expression and clinically relevant data of hepatocellular carcinoma were collected from the Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus database(GEO),respectively.In addition,twenty-one specimens of hepatocellular carcinoma tissues and para-cancerous tissues treated with surgical resection at Qinghai University Affiliated Hospital during 2015-2018 were collected for immunohistochemical detection and Western Blot assays to analyze the expression of SPP2 in HCC.Kaplan-Meier survival and Cox regression analyses were carried out to evaluate the association between SPP2 expression and HCC patient outcome;Approaches to explore the potential mechanisms involved in the immune regulation with SPP2:TIMER database and single sample gene set enrichment analysis(ssGSEA)methods were used for assessing the relationship between SPP2 and immune cell infiltration.Results RNA-Seq data from the TCGA and GEO cohorts showed that SPP2 expression was substantially lower in hepatocellular carcinoma tissue as compared to the para-cancerous tissue and those patients having high expression levels of SPP2 showed a better clinical prognosis.Moreover,the univariate and multivariate COX regression analyses results suggested that SPP2 could serve as a predictor of HCC,independent of other clinical factors.Immunohistochemistry and western blot showed that SPP2 expression was lower in hepatocellular carcinoma tumor tissue than in the para-cancerous tissue,and even lower in high pathological staging.Compared to patients with high SPP2 expression,those with low SPP2 expression had worse overall survival times;Furthermore,immuno-infiltration analysis showed a significant negative correlation between SPP2 expressi
作者
孟永昌
刘川川
王志鑫
庞明泉
冶赓博
董明明
樊海宁
Meng Yongchang;Liu Chuanchuan;Wang Zhixin;Pang Mingquan;Ye Gengbo;Dong Mingming;Fan Haining(Graduate School of Qinghai University,Xining 810016,China;Department of hepatobiliary and pancreatic surgery,Affiliated Hospital of Qinghai University,Xining 810000,China)
出处
《中国高原医学与生物学杂志》
CAS
2023年第2期121-131,共11页
Journal of Chinese High Altitude Medicine & Biology
基金
国家自然科学基金项目(82160466)。
关键词
肝细胞癌
分泌型磷酸蛋白2
预后
免疫浸润
Hepatocellular carcinoma
Secreted phosphoprotein 2
Prognosis
Immune infiltration
