基于生物信息学和免疫组化分析FASN在膀胱癌组织中的表达及临床意义

Expression and clinical significance of FASN in bladder cancer based on bioinformatics analysis and immunohistochemistry

目的:利用生物信息学和免疫组化方法分析脂肪酸合酶(fatty acid synthase,FASN)在膀胱癌组织中的表达及临床意义。方法:利用Oncomine数据库分析FASN mRNA在正常膀胱组织和膀胱癌组织中的表达差异,并进行Meta分析;收集2019年01月至2021年03月在我院泌尿外科行手术治疗的86例膀胱癌患者的手术切除组织石蜡切片,利用免疫组化法检测FASN蛋白在膀胱癌组织和相应癌旁组织中的表达,并分析其与膀胱癌患者若干临床病理特征的关系;利用LinkedOmics数据库分析FASN mRNA表达与临床病理特征的关系;结合免疫组化和病历资料分析FASN蛋白表达与临床病理特征的关系;基于UALCAN和LinkedOmics平台分析该基因与膀胱癌患者生存的关系;基于LinkedOmics和Metascape平台做富集分析;String数据库构建蛋白互作网络。结果:与正常膀胱组织相比,FASN mRNA在膀胱癌组织中的表达显著增加(P<0.05)。免疫组化结果提示FASN蛋白在膀胱癌组织中显著增加。FASN mRNA的表达与膀胱癌患者的肿瘤纯度和年龄相关(P<0.05),而与病理分级和TNM分期无关(P>0.05)。FASN蛋白的表达与膀胱癌患者的年龄和性别有关(P<0.05),而与病理分级、肌层浸润和淋巴结转移无关(P>0.05)。在膀胱癌患者中,FASN高表达者的总生存期要明显低于FASN低表达者(P<0.05)。FASN正相关基因主要与SREBF激活基因表达、辅酶A代谢、细胞脂质分解代谢过程、激素分泌等有关。结论:FASN在膀胱癌组织中高表达,并且与膀胱癌患者的不良预后有关,FASN可能成为膀胱癌诊治的新的生物标志物。

Objective:To analyze the expression and clinical significance of fatty acid synthase(FASN)in bladder cancer by bioinformatics methods and immunohistochemistry.Methods:The differential expressions of FASN mRNA in bladder cancer tissues and normal bladder tissues were analyzed by using Oncomine database,and Meta-analysis was performed.The paraffin-embedded specimens of 86 patients with bladder cancer undergoing surgery from January 2019 to March 2021 were collected.The expressions of FASN protein in badder cancer and para-cancerous tissues were detected by immunohistochemical staining,and the relationship between FASN protein expression and several clinicopathological characteristics was analyzed.The relationship between FASN mRNA expression and clinicopathological characteristics was analyzed by using LinkedOmics database.The relationship between FASN and the survival of bladder cancer patients was analyzed based on UALCAN and LinkedOmics databases.Enrichment analysis was performed based on LinkedOmics and Metascape databases.Constructed a protein-protein interaction network by using String database.Results:Compared with normal bladder tissues,the expression level of FASN mRNA was higher in bladder cancer tissues.Immunohistochemical examination showed that FASN protein was highly expressed in bladder cancer tissues.The expression of FASN mRNA in bladdder cancer patients was correlated with tumor purity and years to birth(P<0.05),but not with pathological grade and TNM stage(P>0.05).The expression of FASN protein in bladdder cancer patients was correlated with age and gender(P<0.05),but not with pathological grade,myometrial infiltration and lymph node metastasis(P>0.05).The overall survival of bladder cancer patients with high expression of FASN was significantly lower than that of patients with low expression(P<0.05).FASN-positively correlated genes were mainly associated with signaling pathways such as activation of gene expression by SREBF,coenzyme A metabolic process,cellular lipid catabolic process and hormone secretion.Conclusion:FASN is over-expressed in bladder cancer tissues,and is associated with poor prognosis.FASN could a new biomarker for the diagnosis and treatment of bladder cancer.