泛癌中分析PVR基因对免疫细胞浸润及患者预后的影响

Pan-cancer analysis of the effect of PVR gene on immune cells infiltration and patients prognosis

脊髓灰质炎病毒受体(poliovirus receptor,PVR)基因与肿瘤的发生发展密切相关,然而PVR在肿瘤免疫中的调控作用及机制尚未阐明。研究从泛癌角度分析PVR在不同类型癌症组织中的表达及与患者预后和免疫水平的关联。通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)和TIMER数据库完成了PVR在癌症和正常组织中表达差异的分析,利用生存分析工具评估了PVR与癌症患者预后的关联。通过TIMER数据库和R软件包评估了PVR在泛癌中与免疫细胞浸润、免疫检查点(immune checkpoint,ICP)基因的共表达关系及癌症基质/免疫评分。为进一步了解PVR基因在不同癌症中的潜在生物学作用机制,对PVR进行了单细胞水平测序分析和基因集富集分析(Gene Set Enrichment Analysis,GSEA);通过qRT-PCR对PVR在多种癌症细胞系中的表达进行验证。结果显示,PVR在肿瘤组织与正常组织中表达具有显著差异,如膀胱尿路上皮癌、胆管癌、结肠癌、食管癌和头颈部癌等。PVR的异常表达与多种癌症的不良预后有关,如肾上腺皮质癌、膀胱尿路上皮癌、乳腺癌和宫颈癌等。PVR的表达水平与泛癌中免疫细胞浸润、基质/免疫评分和ICP基因的表达调控显著相关(均P<0.05,具体见正文)。单细胞测序结果显示,PVR与肿瘤细胞的分化、基因沉默和DNA修复等多种细胞生物学功能和表型有关。GSEA结果发现,PVR与多种肿瘤细胞的免疫相关功能和信号通路有关。qRT-PCR结果显示,相较于健康细胞,PVR在胃癌、结肠癌和肝癌细胞系中表达较高。较全面的泛癌分析表明,PVR是一种癌症组织中高表达并导致较差预后的癌基因,PVR可能是新的免疫依赖的预后预测标志物,能为癌症的靶向治疗提供新方向。

The poliovirus receptor(PVR)gene is closely related to tumorogenesis and development,while the regulatory roles and mechanisms of PVR in tumor immunity are not fully elucidated.This study analyzed the expression of PVR in different types of tumor tissues from a pan-cancer perspective and its correlation with patients prognosis and immunity.The analysis of the expression differences of PVR between cancerous and normal tissues was based on The Cancer Genome Atlas(TCGA)and TIMER database,and the correlation between PVR and the prognosis of cancer patients was assessed using survival analysis tools.Expression analyses of PVR in various with immune cells infiltration,immune checkpoint(ICP)genes expression and stromal/immune scoring were evaluated by the TIMER database and R software.To further understand the potential biological mechanisms of PVR in various cancers,single-cell level sequencing and Gene Set Enrichment Analysis(GSEA)were performed.The expression of PVR was verified by qRT-PCR in a variety of cancer cell lines.The results showed that,compared to that of normal tissues,PVR was significantly differentially expressed in tumor tissues like bladder urothelial carcinoma,cholangiocarcinoma,colon adenocarcinoma,esophageal carcinoma,and head&neck squamous cell carcinoma,etc.Aberrant expression of PVR was associated with poor prognosis for multiple cancers including adrenocortical cancer,bladder urothelial carcinoma,breast invasive carcinoma,and cervical carcinoma,etc.PVR expression was significantly correlated with immune cells infiltration,stromal/immune scoring and the regulation of ICP genes expression on pan-cancer level(all with P<0.05).Single-cell sequencing outcomes showed that PVR was associated with tumor cells multiple cytobiological functions and phenotypes,including cell differentiation,gene silencing and DNA repairing.GSEA revealed that PVR was engaged in immune-related functions and signaling pathways in multiple tumor cells.The qRT-PCR results showed that PVR was highly expressed in stomach,colon and hepatocellular carcinoma cell lines compared to healthy cells.This comprehensive pan-cancer analysis suggests that PVR is an oncogene highly expressed in tumor tissues and leads to poor prognosis.Therefore,PVR may be a new immune-dependent prognosis-predicting marker that may provide new directions for targeted oncotherapy.