Department of Rehabilitation, Tianjin Hospital, Tianjin, China.
Department of Orthopedics, Tianjin Hospital, Tianjin, China.
Biomed Res Int. 2022 Jul 7;2022:2309339. doi: 10.1155/2022/2309339. eCollection 2022.
Lower-grade glioma (LGG) is a crucial pathological type of glioma. Prokineticins have not been reported in LGG. Prokineticins as a member of the multifunctional chemokine-like peptide family are divided into two ligands: PROK1 and PROK2. We evaluated the role of PROK1 and PROK2 in LGG using TCGA database. We downloaded the datasets of LGG from TCGA and evaluated the influence of prokineticins on LGG survival by survival module. Correlations between clinical information and prokineticins expression were analyzed using logistic regression. Univariable survival and multivariate Cox analysis was used to compare several clinical characteristics with survival. Correlation between prokineticins and cancer immune infiltrates was explored using CIBERSORT and correlation module of GEPIA. We analyzed genes of PROK1 and PROK2 affecting LGG, screened differentially expressed genes (DEGs), interacted protein-protein with DEGs through the STRING website, then imported the results into the Cytospace software, and calculated the hub genes. To analyze whether hub genes and prokineticins are related, the relationship between PROK1 and PROK2 and hub genes was assessed and shown by heat map. In addition, gene set enrichment analysis (GSEA) was performed using the TCGA dataset. The univariate analysis using logistic regression and PROK1 and PROK2 showed opposite expression differences between tumor and normal tissues ( < 0.05). PRO1 and PROK2 expressions showed significant differences in tumor grade, age, Iiscitrate DeHydrogenase (IDH) status, histological type, and 1P/19q codeletion. Multivariate analysis revealed that the up-regulated PROK1 and PROK2 expression is an independent prognostic factor for bad prognosis. Specifically, prokineticin expression level has significant correlations with infiltrating levels of Th1 cells, NK CD 56bright cells, and Mast cells in LGG. We screened 21 DEGs and obtained 5 hub genes (, , , , ). GSEA-identified FCMR activation, creation of C4 and C2 activators, and CD22-mediated BCR regulation in gene ontology (GO) were differentially enriched in high PROK1 and PROK2 expression phenotype pathway, cytoplasmic ribosomal proteins, and ribosome and were differentially enriched in the low PROK1 and PROK2 expression phenotype pathway. Prokineticins are a prognostic biomarker and the correlation between hub genes and LGG requires further attention.
低级别胶质瘤（LGG）是胶质瘤的重要病理类型。促动力素在 LGG 中尚未报道。促动力素作为多功能趋化因子样肽家族的一员，分为两个配体：PROK1 和 PROK2。我们使用 TCGA 数据库评估 PROK1 和 PROK2 在 LGG 中的作用。我们从 TCGA 下载了 LGG 数据集，并通过生存模块评估了促动力素对 LGG 生存的影响。使用逻辑回归分析临床信息与促动力素表达的相关性。使用单变量生存和多变量 Cox 分析比较了几种临床特征与生存的关系。使用 CIBERSORT 和 GEPIA 的相关性模块探索了促动力素与癌症免疫浸润的相关性。我们分析了影响 LGG 的 PROK1 和 PROK2 基因，筛选差异表达基因（DEGs），通过 STRING 网站与 DEGs 进行蛋白-蛋白相互作用，然后将结果导入 Cytospace 软件，并计算出枢纽基因。为了分析枢纽基因和促动力素是否相关，通过热图评估和显示 PROK1 和 PROK2 与枢纽基因的关系。此外，使用 TCGA 数据集进行基因集富集分析（GSEA）。逻辑回归和 PROK1 和 PROK2 的单变量分析显示肿瘤组织和正常组织之间的 PRO1 和 PROK2 表达存在相反的差异（<0.05）。PRO1 和 PROK2 的表达在肿瘤分级、年龄、异柠檬酸脱氢酶（IDH）状态、组织学类型和 1P/19q 缺失方面存在显著差异。多变量分析显示，上调的 PROK1 和 PROK2 表达是预后不良的独立预后因素。具体而言，促动力素表达水平与 LGG 中 Th1 细胞、NK CD56bright 细胞和肥大细胞的浸润水平呈显著相关性。我们筛选了 21 个 DEGs，获得了 5 个枢纽基因（,,,, ）。GSEA 鉴定的 FCMR 激活、C4 和 C2 激活剂的产生以及 CD22 介导的 BCR 调节在基因本体论（GO）中在高 PROK1 和 PROK2 表达表型途径、细胞质核糖体蛋白和核糖体中差异富集，在低 PROK1 和 PROK2 表达表型途径中差异富集。促动力素是一种预后生物标志物，枢纽基因与 LGG 的相关性需要进一步关注。
