PLA2G2D在卵巢浆液性腺癌组织中的表达及与患者预后的关系研究  

Increased PLA2G2D Expression Mediates Better Prognosis in Patients With Ovarian Serous Cystadenocarcinoma

作　　者：刘南南 陈红[1] 孙伟娜[1] 杨清清 LIU Nan-nan;CHEN Hong;SUN Wei-na;YANG Qing-qing(Department of Obstetrics and Gynecology,The People's Hospital of Danyang,Affiliated Danyang Hospital of Nantong University,Jiangsu Zhenjiang 212300,China)

机构地区：[1]丹阳市人民医院妇产科,南通大学附属丹阳医院,江苏镇江212300

出　　处：《循证医学》2024年第5期312-320,共9页The Journal of Evidence-Based Medicine

基　　金：江苏省卫健委医学科研面上项目(H2023042)。

摘　　要：目的分析磷脂酶A2组ⅡD(phospholipase A2 groupⅡD,PLA2G2D)在卵巢浆液性腺癌(ovarian serous cystadenocarcinoma,OSC)患者中表达特征、预后价值及临床意义。方法选取2019年1月至2022年1月在丹阳市人民医院手术治疗的65例OSC患者。通过多种公共数据库和免疫组织化学(immunohistochemistry,IHC)分析PLA2G2D在OSC中表达特征及预后价值。通过TIMER 2.0数据库分析OSC中PLA2G2D表达与肿瘤浸润性免疫细胞间关联。通过Pearson检验分析PLA2G2D共表达基因,并进行功能富集信号通路分析。基于TCGAOSC队列构建预测OSC患者预后列线图。基于Kaplan-Meier构建65例OSC患者生存曲线,使用单因素和多因素Cox回归分析临床变量与预后间的关联。结果PLA2G2D RNAseq和蛋白水平在OSC组织中表达增高且患者总体生存率更高(P<0.05)。OSC中PLA2G2D RNAseq表达与巨噬细胞(r=0.472)、树突状细胞(r=0.331)和NK细胞(r=0.274)呈显著正相关性,与B细胞(r=−0.194)和中性粒细胞(r=−0.125)呈负相关性,差异均有统计学意义(P<0.05)。PLA2G2D富集于炎症反应、白细胞活化和免疫反应正向调节等信号通路。基于TCGA-OSC队列构建的列线图能有效预测OSC患者1年、3年和5年生存率。PLA2G2D高表达组患者5年总生存率(overall survival,OS)和无复发生存率(recurrence-free survival,RFS)高于低表达组(P<0.001)。多因素Cox风险回归结果显示PLA2G2D表达是OSC患者DFS[风险比(hazard ratio,HR)=0.412,95%可信区间(confidence interval,CI)0.253~0.672,P<0.001]和OS(HR=0.354,95%CI 0.173~0.724,P=0.004)的独立影响因素。结论PLA2G2D在OSC中高表达且与更好预后相关,这可能与其调控肿瘤微环境中免疫细胞浸润丰度有关,提示PLA2G2D可能作为OSC患者的潜在预后生物标志物及治疗靶点。Objective To analyse the expression characteristics,prognostic value and clinical significance of phospholipase A2 groupⅡD(PLA2G2D)in patients with ovarian serous cystadenocarcinoma(OSC).Methods Sixtyfive OSC patients were selected,who were surgically treated in The People's Hospital of Danyang between January 2019 and January 2022.PLA2G2D expression characteristics and prognostic value in OSC were analysed by various public databases and immunohistochemistry(IHC).The association between PLA2G2D expression and tumour-infiltrating immune cells in OSC was analysed by TIMER2.0 database.PLA2G2D co-expressed genes were analysed by Pearson's test and functionally enriched signalling pathways were analysed.Predictive OSC patient prognostic column line plot was constructed based on the TCGA-OSC cohort.Survival curves for 65 OSC patients were constructed based on Kaplan-Meier,and associations between clinical variables and prognosis were analysed using univariate and multivariate Cox regression.Results PLA2G2D RNAseq and protein levels were increased in OSC tissues and overall patient survival was higher(P<0.05).PLA2G2D RNAseq expression in OSC showed a significant positive correlation with macrophages(r=0.472),dendritic cells(r=0.331)and NK cells(r=0.274)and a negative correlation with B cells(r=−0.194)and neutrophils(r=−0.125),all of which were statistically significant(P<0.05).PLA2G2D was enriched in signalling pathways such as inflammatory response,leukocyte activation and positive regulation of immune response.Column line graphs constructed based on the TCGA-OSC cohort were effective in predicting 1-,3-,and 5-year survival of OSC patients.The 5-year overall survival(OS)and recurrence-free survival(RFS)of patients in the PLA2G2D high-expression group was higher than that of the low-expression group(P<0.001).The results of multifactorial Cox risk regression showed that PLA2G2D expression was an independent influencing factor for DFS[hazard ratio(HR)=0.412,95%confidence interval(CI)0.253~0.672,P<0.001]and OS(HR=0.

关 键 词：卵巢浆液性腺癌 PLA2G2D 肿瘤微环境 列线图 预后 

分 类 号：R737.31[医药卫生—肿瘤]