GPR27基因在卵巢癌组织中的表达及其与肿瘤免疫浸润及患者预后的相关性  

Expression of GPR27 in ovarian cancer and its correlation with tumor immune invasion and prognosis

作　　者：陈瑞娇 史利霞 王艺璇 张韶华 王赞宏[1] CHEN Ruijiao;SHI Lixia;WANG Yixuan;ZHANG Shaohua;WANG Zanhong(Department of Gynaecology and Obstetrics,Third Hospital of Shanxi Medical University,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Taiyuan 030032,China)

机构地区：[1]山西医科大学第三医院妇产科,山西白求恩医院,山西医学科学院,同济山西医院妇产科,太原030032

出　　处：《山西医科大学学报》2023年第4期432-439,共8页Journal of Shanxi Medical University

基　　金：中央引导地方科技发展资金项目(YDZJSX2022B012);山西省科技成果转化引导专项二批项目(201604D132043);山西省基础研究计划项目(202103021224352)。

摘　　要：目的应用生物信息学方法探讨GPR27基因在卵巢癌组织中的表达,并分析其与肿瘤免疫浸润及患者预后的关系。方法在人类蛋白质图谱数据库(human protein atlas,HPA)、基因表达谱交互分析数据库(gene expression profiling interactive analysis,GEPIA)中检索GPR27在卵巢癌中的表达情况;收集2011年1月至2016年12月在山西白求恩医院治疗的卵巢癌患者150例及因子宫平滑肌瘤进行全子宫+双侧附件切除的患者23例,采用免疫组化SP法检测GPR27蛋白的表达,比较GPR27基因在卵巢癌组织与正常卵巢组织中的表达差异,并分析GPR27蛋白表达与卵巢癌患者临床病理特征之间的关系;通过χ^(2)检验、COX风险回归分析筛选影响卵巢癌患者总生存期的独立危险因素,并采用Kaplan-Meier法绘制生存曲线。在Kaplan-Meier plotter,GEPIA在线数据库中检索GPR27对卵巢癌患者生存期的影响。Coexpedia数据库筛选GPR27基因的共表达基因,并将其在WebGestalt中进行富集分析,了解其可能涉及的分子通路;在肿瘤免疫评估资源数据库(tumor immune estimation resource,TIMER)中分析GPR27基因在卵巢癌组织中的表达与肿瘤微环境中的6种免疫细胞的相互关系。结果GPR27基因在卵巢癌组织中呈现高表达,与正常卵巢组织中表达差异具有统计学意义(P<0.05),且GPR27的表达水平与卵巢癌FIGO分期、残留病灶是否达R0、有无腹水相关(P<0.05)。进一步COX风险回归模型分析显示,GPR27高表达是卵巢癌总生存的独立危险因素(P<0.05)。GPR27基因的共表达基因有PROK2、EIF4E3、NFE2L3、A1CF和FUT6,并富集于多种细胞基本生物学功能的通路上。利用TIMER分析得出GPR27基因与卵巢癌中中性粒细胞、巨噬细胞和树突状细胞的浸润情况呈显著负相关(P<0.05)。结论GPR27基因在卵巢癌组织中高表达,其可能通过破坏肿瘤微环境中免疫细胞的浸润影响患者预后。Objective To investigate the expression of GPR27 gene in ovarian cancer by bioinformatics method,and analyze its relationship with tumor immune infiltration and prognosis.Methods The expression of GPR27 in ovarian cancer was investigated in HPA and GEPIA online databases.From January 2011 to December 2016,150 patients with ovarian cancer and 23 patients with total uterus plus bilateral adnexectomy due to uterine leiomyoma were collected from Shanxi Bethune Hospital.The expression of GPR27 protein was detected and compared between ovarian cancer and normal ovarian tissue by immunohistochemical SP method,and the relationships between GPR27 protein expression and clinicopathologic features of ovarian cancer patients were analyzed.Independent risk factors affecting the overall survival of ovarian cancer patients were screened by single and multiple factors,and the survival curve was drawn by Kaplan-Meier method.Effects of GPR27 on survival of ovarian cancer patients were analyzed based on Kaplan-Meier plotter,GEPIA online databases.The co-expressed genes of GPR27 gene were screened in Coexpedia database and enriched in Webgestalt to understand the possible molecular pathways.The correlation between the expression of GPR27 gene in ovarian cancer tissue and six kinds of immune cells in the tumor microenvironment was analyzed based on TIMER database.Results The expression of GPR27 gene was highly expressed in ovarian cancer tissues,statistically higher than that in normal ovarian tissues(P<0.05),and the expression level of GPR27 was correlated with the FIGO stage of ovarian cancer,no gross residual lesion(R0),and the incidence of ascites(P<0.05).Further COX regression model analysis suggested that high expression of GPR27 was an independent risk factor for overall survival of ovarian cancer(P<0.05).The co-expressed genes of GPR27 gene were PROK2,EIF4E3,NFE2L3,A1CF and FUT6,which were enriched in a variety of basic biological function pathways of cells.TIMER analysis showed that GPR27 gene was significantly negatively co

关 键 词：卵巢癌 GPR27基因 肿瘤微环境 肿瘤免疫浸润 预后 

分 类 号：R737.31[医药卫生—肿瘤]