PDLIM2对前列腺癌预后影响的生物信息学分析

Bioinformatic analysis of PDLIM2 expression on prognosis of prostate cancer

目的应用生物信息学技术分析PDLIM2对前列腺癌(PCa)预后的影响,并深度挖掘其基因功能。方法利用UCSC Xena数据库下载癌症基因组图谱PCa数据,分析并验证PCa组织与癌旁正常组织中PDLIM2表达差异,比较PDLIM高、低表达组患者总生存期(OS)和无进展生存期(PFS)。利用Linked Omics数据库对PDLIM2共表达基因进行基因本体富集分析,利用相关数据库基因模块分析PDLIM2与肿瘤免疫细胞浸润程度、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、免疫检查点(ICP)基因表达及肿瘤干性评分的相关性。结果与癌旁正常组织相比,PCa组织中PDLIM2 mRNA表达水平较低(P<0.05),而PDLIM2启动子区域甲基化水平较高(P<0.05);且PCa组织中PDLIM2 mRNA表达水平与Gleason评分、分子分型均有关(均P<0.05)。生存分析显示,PDLIM2高表达者PFS明显短于PDLIM2低表达者(P<0.05);而PDLIM2高、低表达者OS比较,差异无统计学意义(P>0.05)。PDLIM2 mRNA表达与TSPAN4、LGALS1、GAS6、GYPC、LYL1等12198个基因均呈正相关(均P<0.05),与SMARCC1、HOOK1、ZNF24、DNAJC16、FOXA1等7852个基因均呈负相关(均P<0.05)。与PDLIM2相关的基因主要富集在胶原代谢过程、整合素介导的信号通路、体液免疫反应、白细胞迁移、IFN-γ产生、急性炎症反应、血管生成等生物学过程。PCa组织中PDLIM2 mRNA表达水平与肿瘤免疫细胞浸润程度、TMB、MSI、38个ICP基因表达及肿瘤干性评分均呈正相关(均P<0.05)。结论PDLIM2可能成为评估PCa预后的生物学标志物和肿瘤免疫治疗的新靶点。

Objective To analyze the correlation between PDLIM2 expression and prognosis in prostate cancer(PCa)based on bioinformatics,and to explore their functions.Methods The RNA-seq data for PCa was downloaded from UCSC Xena database.The PDLIM2 mRNA expression levels were assessed in PCa cancer and adjacent normal tissues.The overall survival(OS)and progress free survival(PFS)were compared between PCa patients with high and low PDLIM2 expression.Gene ontology enrichment analysis of genes coexpressed with PDLIM2 was conducted via Linked Omics.Meanwhile,the correlations between PDLIM2 expression and immune cell infiltration patterns,tumor mutation burden(TMB),microsatellite instability(MSI),immune checkpoint(ICP)molecules,and tumor stemness were explored.Results PDLIM2 mRNA expression was downregulated in PCa tissues compared with the adjacent normal tissues(P<0.05).Higher PDLIM2 promoter methylation levels in PCa were observed compared to the adjacent normal tissues(P<0.05).Increased PDLIM2 mRNA expression correlated with high Gleason score and molecular subtypes of PCa.The PFS was significantly shorter in PCa patients with PDLIM2-high expression than in patients with PDLIM2-low expression(P<0.05).However,there was no statistically difference in OS(P>0.05).The results showed that PDLIM2 mRNA expression was positively correlated with 12198 genes(such as TSPAN4,LGALS1,GAS6,GYPC,LYL1,et al.)and negatively correlated with 7852 genes(such as SMARCC1,HOOK1,ZNF24,DNAJC16,FOXA1,et al.).Gene functional enrichment analyses of biological process showed that collagen metabolic process,humoral immune response,leukocyte migration,acute inflammatory response,regulation of cell activation,interferon-gamma production,and angiogenesis were significantly enriched.The analysis on PDLIM2 functions in PCa suggested that the ex-pression level of PDLIM2 mRNA was correlated with immune cells infiltration,TMB,MSI,ICP genes,and the tumor stemness in PCa tissues.Conclusion PDLIM2 may be a biomarker for evaluating the prognosis of PCa and a new target for tumor immunotherapy.