基于前列腺癌骨转移BMP相关差异表达基因预测前列腺癌患者的转移复发  

Prediction of metastatic and recurrence in prostate cancer patients based on BMP-related differential gene in prostate cancer bone metastases

作　　者：邱蘜 胡建鹏[1] QIU Ju;HU Jianpeng(Department of Urology,the Affiliated People s Hospital of Jiangsu University,Zhenjiang Jiangsu 212002,China)

机构地区：[1]江苏大学附属人民医院泌尿外科,江苏镇江212002

出　　处：《江苏大学学报（医学版）》2024年第6期522-531,541,共11页Journal of Jiangsu University：Medicine Edition

基　　金：江苏省卫生健康委科研项目(M2021038)。

摘　　要：目的:基于生物信息学方法构建预测前列腺癌(PCa)骨转移的预后风险模型,探究风险评分对预后和免疫浸润的影响。方法:从基因表达公共数据库(GEO)下载PCa患者的临床资料和微阵列表达数据,分子特征数据库(MSigDB)下载骨形成蛋白(BMP)通路相关基因。通过差异分析筛选出PCa骨转移样本与原发性PCa样本的差异表达基因(differential expression genes,DEGs),与BMP通路相关基因取交集得到BMP相关DEGs,通过LASSO回归分析筛选风险基因构建预后风险模型,多因素Cox回归分析筛选PCa独立预后因素。根据风险模型计算患者的风险评分,并以中位值分为高危组和低危组,识别DEGs进行功能富集分析,比较高危、低危组间的免疫浸润差异。结果:从3055个PCa骨转移样本中的DEGs与BMP相关基因集取交集后得到13个BMP相关DEGs,通过LASSO回归筛选出4个基因标签构建预后风险模型,其中分泌型卷曲相关蛋白2(SFRP2)、内皮糖蛋白(ENG)、卵泡素样蛋白1(FSTL1)是风险基因,脊索素样蛋白1(CHRDL1)是保护基因。根据风险评分中位值(7.3)将PCa患者分为高危和低危组,Kaplan-Meier分析显示高危组患者无转移生存期及无生化复发生存期明显低于低危组患者。高危组患者更容易发生骨转移和生化复发,且风险评分与前列腺特异性抗原(PSA)值、Gleason评分及T分期呈正相关。高危组上调基因主要参与WNT/BMP信号通路的激活,明显富集在上皮细胞增殖、细胞外基质等生物过程;GSEA分析显示,差异基因在间充质转化、炎症反应、血管生成以及多个肿瘤转移基因集中上调。免疫浸润分析显示高危组患者拥有更高的免疫细胞浸润程度、肿瘤相关成纤维细胞(CAFs)、巨噬细胞、Estimate评分、基质评分及免疫评分,而肿瘤纯度低于低危组。结论:基于LASSO回归分析构建的BMP相关DEGs预后风险模型能够有效预测PCa骨转移发生,且高风险评分与PCa患者预�Objective:To construct a prognostic risk model for predicting bone metastasis in prostate cancer(PCa)based on bioinformatics approach,and to investigate the effect of risk score on prognosis and immune infiltration.Methods:Clinical information and microarray expression data of PCa patients were downloaded from the Gene Expression Omnibus(GEO),and genes related to the bone morphogenetic protein(BMP)pathway were downloaded from the Molecular Signature Database(MSigDB).The differential expression genes(DEGs)of PCa bone metastasis samples and primary PCa samples were screened by differential analysis,and the intersection with BMP pathway-related genes was taken to obtain BMP-related DEGs,and the prognostic risk model was constructed by screening risk genes through LASSO regression analysis,and independent prognostic factors of PCa were screened by multifactorial regression analysis.The risk scores of patients were calculated according to the risk model and subsequently divided into two groups of high and low risk scores by corresponding score median values,and DEGs were identified for functional enrichment analysis to compare the differences in immune infiltration between high and low risk groups.Results:After the intersection of DEGs and BMP-related gene sets in 3055 differentially expressed genes of PCa bone metastasis samples,13 BMP-related DEGs were obtained.Four gene were screened by LASSO regression to construct a prognostic risk model,in which secreted frizzled-related proteins 2(SFRP2),endoglin(ENG),and follistatin-like protein 1(FSTL1)were risk genes and chordin like 1(CHRDL1)was a protective gene.Kaplan-Meier analysis showed that metastasis-free survival and biochemical recurrence-free survival of patients in the high-risk group were significantly lower than that of patients in the low-risk group.Multifactorial regression analysis identified risk score as an independent prognostic factor for PCa bone metastasis,and patients in the high-risk group were more likely to develop bone metastasis and biochemical r

关 键 词：前列腺癌 骨转移 BMP信号通路 预后风险模型 免疫浸润 

分 类 号：R737.25[医药卫生—肿瘤]