摘要
目的通过生物信息学方法探讨肾透明细胞癌(cc RCC)中脂肪酸合酶(FASN)基因和蛋白的表达水平及其与肿瘤免疫细胞浸润的相关性。方法从癌症基因组图谱数据库检索FASN与cc RCC相关的表达谱数据,通过UALCAN数据库分析cc RCC中FASN基因表达水平及其与cc RCC患者临床病理分期、分级的相关性,使用基因表达谱动态分析网站分析FASN基因与cc RCC患者预后的相关性,使用人蛋白图谱数据库分析人组织中FASN蛋白表达水平,使用肿瘤免疫评估数据库和肿瘤微环境数据库分析FASN与肿瘤免疫的相关性,使用基因注释和分析数据库对FASN及相关基因进行功能富集分析。结果在不同病理分期、分级cc RCC中FASN基因表达水平均显著高于正常组织,FASN基因高表达的患者预后较差。FASN蛋白S207和S2198位点磷酸化水平在cc RCC中显著降低。FASN表达与cc RCC中CD8^(+)T免疫细胞浸润水平呈负相关,与调节性T细胞浸润水平呈正相关,免疫治疗会影响FASN与免疫细胞在cc RCC中共定位。FASN主要参与细胞脂质代谢、甾醇调节元件结合转录因子1激活基因表达、过氧化物酶体增殖物激活受体信号通路、脂肪酸生物合成等生物功能。结论FASN在cc RCC中高表达,且与cc RCC患者临床预后、肿瘤免疫细胞浸润相关。
Objective To investigate the gene and protein expression levels of fatty acid synthase(FASN)in clear cell renal cell carcinoma(ccRCC)and its correlation with tumor immune cell infiltration by bioinformatic methods.Methods The expression profile data of FASN were obtained from the TCGA database,and the analysis of the differential expression levels of FASN in ccRCC and the correlation between FASN and clinicopathological factors of ccRCC patients were performed using the R language and the bioinformatics database of the UALCAN database,a comprehensive cancer histology analysis portal.The GEPIA2 website,a website for dynamic analysis of gene expression profiles,was used to analyze the prognostic relevance of FASN in patients with ccRCC.The Human Protein Atlas database was used to analyze the protein expression levels of FASN in tissues and organs.Further more,the tumor-immune interaction analysis databases TIMER2 and the tumor microenvironment database,were used to explore the relational relevance between FASN and tumor immune infiltration.The gene annotation and analysis database Metascape,were used to analyze the functional enrichment of FASN and related genes.Results The gene expression levels of FASN were significantly higher in different tumor stages and grades of ccRCC than that in paracancerous tissues,and patients with high FASN expression had a poorer survival prognosis.Phosphorylation of the FASN proteins at S207 and S2198 were significantly reduced in ccRCC.FASN expression was negatively correlated with the level of CD8^(+)T immune cell infiltration in ccRCC tumors and positively correlated with regulatory T cells,and immunotherapy affected FASN co-localization with immune cells in ccRCC.FASN is mainly involved in lipid metabolism,sterol regulatory element binding factor 1 activation gene expression,peroxisome proliferator-activated receptor signaling pathway,and fatty acid biosynthesis.Conclusions FASN is upregulated in ccRCC and correlated with ccRCC clinical prognosis and tumor immune cell infiltratio
作者
张琳
王东文
吴波
ZHANG Lin;WANG Dongwen;WU Bo(First Clinical Medical College of Shanxi Medical University,Taiyuan 030001,China;不详)
出处
《现代泌尿生殖肿瘤杂志》
2023年第4期197-202,207,共7页
Journal of Contemporary Urologic and Reproductive Oncology
基金
国家自然科学基金(81970662)
山西省“1331工程”重点创新团队建设计划(3c332019001)
国家癌症中心重点课题(SZ2020ZD-003)
山西省研究生教育创新项目(2023SJ142)
山西省基础研究计划(20210302123242)
北京白求恩公益基金会,泌尿肿瘤专项研究基金(mnzl202029)。
关键词
脂肪酸合酶
肾透明细胞癌
预后分析
生物信息学
免疫浸润
Fatty acid synthase
Kidney renal clear cell carcinoma
Prognostic analysis
Bioinformatics methods
Immune infiltration
