脂肪非典型钙黏蛋白1基因在胰腺癌中的表达及临床意义  

Expression and clinical significance of FAT1 gene in pancreatic adenocarcinoma

作　　者：刘鑫源 杨莹 杨朝丹 马政霄 吴聪慧 徐陈 朱蕊 刘盼 应莉莎[3] 尹文娟[3] 苏丹 Liu Xinyuan;Yang Ying;Yang Chaodan;Ma Zhengxiao;Wu Conghui;Xu Chen;Zhu Rui;Liu Pan;Ying Lisha;Yin Wenjuan;Su Dan(The Second Clinical Medical College,Zhejiang Chinese Medicine University,Hangzhou 310053,China;Department of Pathology,Zhejiang Cancer Hospital,Institute of Basic Medicine and Cancer,Chinese Academy of Sciences,Hangzhou 310022,China;School of Molecular Medicine,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,China)

机构地区：[1]浙江中医药大学第二临床医学院,杭州310053 [2]中国科学院大学杭州高等研究院分子医学院,杭州310024 [3]浙江省肿瘤医院、中国科学院杭州医学研究所病理科,杭州310022

出　　处：《中华肿瘤杂志》2024年第11期1029-1037,共9页Chinese Journal of Oncology

基　　金：国家重点研发计划(2021YFA0910100);浙江省领军型创新创业团队建设项目(2022R01006);浙江省医药卫生科技计划青年创新项目(2023RC006)。

摘　　要：目的探讨脂肪非典型钙黏蛋白1(FAT1)基因在胰腺癌中的表达情况及其与胰腺癌的临床病理特征、预后及免疫治疗的关系。方法(1)生物信息学分析:基于癌症基因组图谱(TCGA)数据库中179例胰腺癌的FAT1 mRNA表达和临床数据、基因型-组织表达(GTEx)数据库中328例正常胰腺组织的FAT1 mRNA表达数据,分析胰腺癌和正常胰腺组织中FAT1 mRNA的表达差异及FAT1 mRNA表达与胰腺癌分化程度、临床分期、预后、免疫细胞浸润、免疫检查点关联基因的关系,应用Limma 3.40.2软件包分析FAT1相关差异表达基因,并对差异表达基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。通过人类蛋白质图谱(HPA)数据库分析FAT1在胰腺癌及癌旁组织中免疫组织化学(IHC)染色情况。(2)自有组织样本验证:收集2010年3月8日至2020年9月30日浙江省肿瘤医院收治的192例胰腺导管腺癌患者的组织样本和临床、预后资料,对组织样本进行IHC染色,验证FAT1在胰腺癌中的蛋白表达及其与免疫相关蛋白、胰腺癌分化程度、临床分期、预后的关系。结果(1)生物信息学分析:来自TCGA数据库的179例胰腺癌组织FAT1 mRNA表达量为5.55±1.04,高于来自GTEx数据库的328例正常胰腺组织FAT1 mRNA的表达量(2.95±0.53,P<0.001)。FAT1特异性IHC染色图像显示,胰腺癌组织FAT1表达普遍较高,且FAT1的表达从细胞膜向细胞质转移。高分化组(31例)、中分化组(96例)和低分化组(52例)FAT1 mRNA表达量分别为4.99±1.46、5.51±0.80和5.68±1.08,均高于正常胰腺组织(均P<0.001),中分化组、低分化组FAT1 mRNA表达量均高于高分化组(均P<0.001)。90例FAT1 mRNA低表达组患者的中位无进展生存时间(PFS)和中位总生存时间(OS)分别为16.5和24个月,均长于89例FAT1 mRNA高表达组(中位PFS和OS分别为13和18个月,P值分别为0.011和0.005)。多因素Cox回归分析显示,FAT1 mRNA表达水平为胰腺癌患者OS�Objective To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features,prognosis,and immunotherapy for pancreatic adenocarcinoma.Methods (1)Bioinformatics analysis:based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database,and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database.We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation,clinical stage,prognosis,immune cell infiltration,and immune checkpoint-associated genes in pancreatic adenocarcinoma.FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package,and GO and KEGG enrichment analysis was performed on the differentially expressed genes.Immunohistochemical(IHC)of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database.(2)Validation of own tissue samples:tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8,2010 to September 30,2020 were collected.IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins,the degree of differentiation of pancreatic adenocarcinoma,clinical staging,and prognosis.Results (1)Bioinformatics analysis:the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04,which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database(2.95±0.53,P<0.001).FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues,and FAT1 expression shifted from the cell membrane to the cytoplasm.The FAT1 mRNA expression in the highly differentiated group(31 cases),the moderately

关 键 词：胰腺肿瘤 脂肪非典型钙黏蛋白1 免疫微环境 预后 生物信息学 

分 类 号：R735.9[医药卫生—肿瘤]