嘌呤能受体在卵巢癌中的预后价值及肿瘤免疫浸润分析

Prognostic Value of Purinergic Receptors in Ovarian Cancer and Analysis of Tumor Immune Infiltration

目的构建浆液性卵巢癌(OV)嘌呤能受体家族基因的预后模型,分析基因的表达与免疫细胞浸润及常用化疗药物的关系。方法下载癌症基因图谱(TCGA)等数据库中15个嘌呤能受体家族基因的表达谱数据及临床信息,利用LASSO回归分析筛选与OV患者生存有关的基因,根据风险值对患者分组并使用Kaplan-Meier Plotter对关键基因进行生存分析。应用多因素Cox回归分析构建基于TCGA-OV数据集的预后模型,绘制列线图和校准曲线。利用TIMER、xCell算法进行免疫浸润分析。利用TIDE算法分析基因的表达与免疫检查点阻断(ICB)治疗的相关性。利用TCGA联合癌症药物敏感性基因组学(GDSC)数据库进行药物敏感性分析。结果LASSO回归分析筛选得到6个嘌呤能受体家族基因与OV患者预后有关。多因素Cox回归分析显示,P2RX6、P2RY12、P2RY14、年龄和种族是OV患者独立的预后因素(P<0.05)。P2RX6和P2RY14在OV中表达下调(P<0.05)。P2RY14的表达不仅与PDCD1、CTLA4、TIGIT等多种免疫检查点有关,还与紫杉醇、顺铂、环磷酰胺、多西他赛的半抑制浓度(IC50)呈负相关。P2RY14相关基因主要参与免疫细胞激活、分化、增殖等生物学过程。结论基于TCGA数据库构建OV患者的预后模型,经筛选得出P2RY14可作为OV患者预后独立危险因素,可为指导OV的免疫治疗提供新的思路和方向。

Objective To construct a prognostic model of purinergic receptor family genes in serous ovarian cancer(OV),and to analyze the relationship between gene expression and immune cell infiltration and commonly used chemotherapeutic drugs.Methods The expression profile data and clinical information of 15 purinergic receptor family genes in databases such as the Cancer Genome Atlas(TCGA)were downloaded.LASSO regression analysis was used to screen genes related to the survival of OV patients.Patients were grouped according to the risk value and Kaplan-Meier Plotter was used to analyze the survival of key genes.Multivariate Cox regression analysis was used to construct a prognostic model based on TCGA-OV data set,and the nomogram and calibration curve were drawn.Immune infiltration analysis was performed using TIMER and xCell algorithms.TIDE algorithm was used to analyze the correlation between gene expression and immune checkpoint blockade(ICB)treatment.Drug sensitivity analysis was performed using the TCGA combined with Genomics of Drug Sensitivity in Cancer(GDSC)database.Results Six purinergic receptor family genes screened by LASSO regression analysis were related to the prognosis of OV patients.Multivariate Cox regression analysis showed that P2RX6,P2RY12,P2RY14,age and race were independent prognostic factors for OV patients(P<0.05).The expression of P2RX6 and P2RY14 was down-regulated in OV(P<0.05).The expression of P2RY14 was not only related to PDCD1,CTLA4,TIGIT and other immune checkpoints,but also negatively correlated with the half inhibitory concentration(IC50)of paclitaxel,cisplatin,cyclophosphamide and docetaxel.P2RY14-related genes were mainly involved in biological processes such as immune cell activation,differentiation,and proliferation.Conclusion Based on the TCGA database,the prognostic model of OV patients is constructed.After screening,P2RY14 can be used as an independent risk factor for the prognosis of OV patients,which can provide new ideas and directions for guiding the immunotherapy of OV.