SIRT7在胰腺癌中的表达及其与免疫浸润水平相关性分析  

Analysis of SIRT7 expression and its correlation with immune infiltration level in pancreatic cancer

作　　者：王首寒 武艳[2] 孙小单[3] WANG Shou-han;WU Yan;SUN Xiao-dan(Department of Abdominal Tumor Surgery, Jilin Cancer Hospital, Changchun 130012, China;Department of Pathology, Jilin Cancer Hospital, Changchun 130012, China;Postdoctoral Research Workstation, Jilin Cancer Hospital, Changchun 130012, China)

机构地区：[1]吉林省肿瘤医院腹部肿瘤外科,吉林长春130012 [2]吉林省肿瘤医院病理科,吉林长春130012 [3]吉林省肿瘤医院博士后工作站,吉林长春130012

出　　处：《河北医科大学学报》2022年第7期775-780,共6页Journal of Hebei Medical University

基　　金：吉林省中医药科技项目(2021095);吉林省卫生健康科技能力提升项目(2021JC097)。

摘　　要：目的探索沉默信息调节因子2同源蛋白7(silent information regulator 2 homolog protein 7,SIRT7)在胰腺癌中的表达及其与肿瘤免疫浸润水平的相关性。方法收集Oncomine数据库和GEPIA数据库中SIRT7 mRNA在胰腺癌中的表达情况。收集27例临床组织标本进行免疫组织化学染色,检测SIRT7蛋白水平表达情况。分析SIRT7与胰腺癌免疫浸润水平的关系。利用cBioPortal平台中胰腺癌样本的RNA测序数据,分析SIRT7基因突变情况。利用STRING数据库预测胰腺癌中与SIRT7相互作用的蛋白并进行基因富集分析。结果Oncomine、GEPIA数据库分析及临床组织标本免疫组织化学结果均显示在胰腺癌组织中SIRT7的转录与蛋白表达水平高于癌旁组织。SIRT7表达水平与胰腺癌肿瘤浸润的效应记忆CD8^(+)T细胞、B细胞、自然杀伤细胞、自然杀伤T细胞等表达呈负相关,与辅助性T细胞17呈正相关。cBioPortal平台检索到的749例胰腺癌样本中13例发生SIRT7基因变异,总变异率为1.73%。组蛋白脱乙酰酶1/2/4/6/8/11(HDAC 1/2/4/6/8/11)、肿瘤蛋白p53、叉头盒转录因子O3等蛋白与SIRT7有明显相互作用,上述蛋白参与了组蛋白去乙酰化、调节DNA转录等多种生物过程,且与细胞周期、Notch等多条肿瘤相关通路有关。结论SIRT7在胰腺癌组织中高表达,与肿瘤免疫浸润水平密切相关,与其相互作用的蛋白参与胰腺癌相关分子通路。SIRT7可能成为胰腺癌诊断、治疗及免疫疗效评估的潜在靶点。Objective To investigate the expression of silent information regulator 2 homolog protein 7(SIRT7)and its correlation with immune infiltration level in pancreatic cancer.Methods The mRNA expression of SIRT7 in pancreatic cancer tissues was collected from Oncomine and GEPIA databases.A total of 27 clinical tissue specimens were collected by immunohistochemical staining,and SIRT7 protein expression was detected.The relationship between SIRT7 expression and immune infiltration level in pancreatic cancer was analyzed.SIRT7 gene mutation landscape was analyzed by cBioPortal based on the RNA sequencing data of pancreatic cancer samples.Proteins interacting with SIRT7 were predicted using the STRING database and gene set enrichment analysis was performed.Results Analyzing data from Oncomine and GEPIA database and the immunohistochemical results from clinical tissue specimens revealed that transcription and protein levels of SIRT7 were both highly expressed in pancreatic cancer tissues compared with adjacent tissues.SIRT7 expression was negatively correlated with the expression of effector memory CD8^(+)T cells,B cells,nature killer cells,nature killer T cells in pancreatic cancer,but positively correlated with the level of T helper cells 17.SIRT7 gene mutation occurred in 13 of 749 pancreatic cancer samples from cBioPortal,with a total mutation rate of 1.73%.Histone deacetylase 1/2/4/6/8/11(HDAC 1/2/4/6/8/11),tumor protein P53(TP53),forkhead box O3(FOXO3)had obvious interactions with SIRT 7.These proteins participated in numbers of biological process such as histone deacetylation and DNA transcription regulation,and were involved in many cancer-related pathways such as cell cycle and Notch.Conclusion SIRT7 is overexpressed in pancreatic cancer tissue,which is closely related to tumor immune infiltration.The proteins interacted with it are involved in numbers of pancreatic cancer-related pathways.SIRT7 may be a potential target for pancreatic cancer diagnosis,treatment and evaluation of immune therapy effect.

关 键 词：胰腺肿瘤 沉默信息调节因子2同源蛋白7 免疫浸润 

分 类 号：R735.9[医药卫生—肿瘤]