基于THPA和TCGA数据分析丙酮酸羧化酶在浆液性卵巢癌组织中的表达和临床意义  

Analysis of pyruvate carboxylase expression in serous ovarian cancer tissues and its clinical significance base on THPA and TCGA database

作　　者：徐苏娟 许鹏飞[1] 徐玲玲[1] XU Sujuan;XU Pengfei;XU Lingling(Department of Gynecology, Nanjing Maternal and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing 210004, China)

机构地区：[1]南京市妇幼保健院,南京医科大学附属妇产医院妇科,南京210004

出　　处：《临床肿瘤学杂志》2021年第4期358-362,共5页Chinese Clinical Oncology

基　　金：国家自然科学基金资助项目(81872379);南京市卫生青年人才项目(QRX17157)。

摘　　要：目的通过人类蛋白质图谱(THPA)和癌症基因组图谱(TCGA)数据库分析丙酮酸羧化酶(PC)在卵巢癌组织中的蛋白表达及与浆液性卵巢癌(SOC)患者预后的关系,初步探讨PC对于卵巢癌肿瘤糖酵解的影响。方法从THPA数据库下载PC在卵巢癌中表达的免疫组织化学切片并分析其光密度值;从TCGA数据库下载SOC患者的临床病理特征数据和PC表达数据。分析PC表达与SOC患者临床病理特征间的关系,Kaplan-Meier法分析SOC组织中PC表达与患者总生存期(OS)的关系,Cox风险比例回归模型进一步分析PC是否为SOC不良预后的独立指标。Pearson相关性分析检测PC表达与OS和糖酵解限速酶(HK2、PFKFB3、PKM2和LDHA)表达的相关性。结果与正常卵巢组织相比,PC在卵巢癌组织中高表达(P<0.05)。PC表达与年龄、FIGO分期、病理分级、肿瘤部位、疾病状态、淋巴浸润、肿瘤状态、生存状态和种族均无关(P>0.05)。与PC低表达的SOC相比,PC高表达者的OS更短,且PC表达越高,其诊断至死亡的时间越短(r=-0.151,P=0.04)。多因素分析显示PC表达是SOC患者预后不良的独立风险因素(HR=3.126,95%CI:1.574~6.209,P=0.001)。PC表达与糖酵解限速酶HK2(r=0.21,P=1.2e-05)、PFKFB3(r=0.22,P=5.6e-06)和PKM2(r=0.31,P=4.8e-11)表达呈正相关。结论PC在卵巢癌组织中过表达且是SOC患者的一个独立不良预后指标。Objective To analyze the protein expression of pyruvate carboxylase(PC)in ovarian cancer tissues and the relationship of PC expression with prognosis of serous ovarian cancer(SOC)patients via The Human Protein Atlas(THPA)and The Cancer Genome Atlas(TCGA)database.Methods Immunohistochemistry data of ovarian cancer from THPA database was downloaded to analyze optical density.Clinical information and PC expression of SOC patients were downloaded from TCGA database.Relationship between PC expression and clinicopathological characteristics of patients with SOC was analyzed.Kaplan-Meier method was applied to analyze relationship between PC expression in SOC and overall survival(OS).Cox proportional hazard regression model was used to further analyze whether PC was an independent indicator of poor prognosis of SOC.Pearson correlation was made to detect the associations of PC with HK2,PFKFB3,PKM2 and LDHA.Results Compared with normal ovary tissues,the protein expression of PC overexpressed in ovarian cancer tissues(P<0.05).However,PC expression level was not associated with age,FIGO stage,pathological grade,tumor location,disease status,lymphatic invasion,tumor status,survival status and race(P>0.05).Kaplan-Meier results suggested that the SOC patients with high expression of PC had a shorter OS(P<0.01).Moreover,PC expression had a negative correction with the death from diagnosis data(r=-0.151,P=0.04).Multivariate analysis showed that PC expression was an independent risk factor for poor prognosis in patients with SOC(HR=3.126,95%CI:1.574-6.209,P=0.001).Beside this,PC expression had a positive correction with the rate-limiting enzyme of aerobic glycolysis including HK2(r=0.21,P=1.2e-05),PFKFB3(r=0.22,P=5.6e-06)and PKM2(r=0.31,P=4.8e-11).Conclusion PC is an important marker of poor prognosis in patients with SOC.

关 键 词：浆液性卵巢癌 丙酮酸羧化酶 预后 糖酵解 

分 类 号：R737.31[医药卫生—肿瘤]