Xie Jian, Qiao Lili, Deng Guodong, Liang Ning, Xing Ligang, Zhang Jiandong
Department of Oncology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China.
Ann Transl Med. 2022 Feb;10(4):227. doi: 10.21037/atm-22-198.
Polycomb group factor 1 (PCGF1) plays a vital role in the self-renewal of cancer stem cells (CSCs). However, the prognostic value and potential function of PCGF1 in glioma progression, especially in tumor immunity, remain unclear.
This study investigated PCGF1 expression in pan-cancers and glioma using The Cancer Genome Atlas Project data, and conducted a logistic regression analysis to analyze the association between PCGF1 expression and the clinicopathological features of glioma patients. Kaplan-Meier and Cox regression analyses were used to assess the prognostic roles of PCGF1. The functional analysis using gene ontology and Kyoto Encyclopedia of Genes and Genomes databases and a gene set enrichment analysis (GSEA) were conducted to examine the PCGF1-related biological processes and signaling pathways. Finally, the roles of PCGF1 in immune infiltration were analyzed by a single sample GSEA (ssGSEA).
PCGF1 expression was upregulated in glioma tissues. The high expression of PCGF1 was significantly associated with an age >60 years (P<0.001), an increased World Health Organization grade (P<0.001), and wildtype isocitrate dehydrogenase (IDH) status (P<0.001), and predicted poor overall survival (OS) [hazards ratio (HR) =2.90, 95% confidence interval (CI): 2.25-3.74; P0.001], the progression-free interval (PFI) (HR =1.99, 95% CI: 1.60-2.46; P0.001), and disease specific survival (DSS) (HR =2.84, 95% CI: 2.18-3.71; P0.001). The multivariate regression analysis confirmed that PCGF1 expression was an independent prognostic factor of OS (HR =1.581, 95% CI: 1.161-2.153; P=0.004). Based on the functional enrichment analysis, we identified the PCGF1-related differentially expressed genes (DEGs), and found that PCGF1 was involved in regulating many oncogenic signaling pathways, such as the phosphatidylinositol 3-kinase and protein kinase B pathway, the Janus kinase/signal transducers and activators of transcription (JKT-STAT) signaling pathway, notch signaling and integrin signaling pathway. In addition, we found that PCGF1 expression was positively associated with the abundance of Th2, but negatively associated with T follicular helper, T central memory, and T gamma delta cells. Additionally, PCGF1 participated in the regulation of numerous immune-related processes in glioma.
PCGF1 is a promising prognostic biomarker, and as it governs cancer-related pathways and tumor immunity, it plays an important role in glioma development.
多梳蛋白家族因子1（PCGF1）在癌症干细胞（CSCs）的自我更新中起着至关重要的作用。然而，PCGF1在胶质瘤进展中的预后价值和潜在功能，尤其是在肿瘤免疫方面，仍不清楚。
本研究使用癌症基因组图谱计划数据调查了PCGF1在泛癌和胶质瘤中的表达，并进行逻辑回归分析以分析PCGF1表达与胶质瘤患者临床病理特征之间的关联。采用Kaplan-Meier和Cox回归分析来评估PCGF1的预后作用。使用基因本体论和京都基因与基因组百科全书数据库进行功能分析以及基因集富集分析（GSEA），以研究与PCGF1相关的生物学过程和信号通路。最后，通过单样本GSEA（ssGSEA）分析PCGF1在免疫浸润中的作用。
PCGF1在胶质瘤组织中表达上调。PCGF1的高表达与年龄>60岁（P<0.001）、世界卫生组织分级增加（P<0.001）以及野生型异柠檬酸脱氢酶（IDH）状态（P<0.001）显著相关，并预测总生存期（OS）较差[风险比（HR）=2.90，95%置信区间（CI）：2.25 - 3.74；P<0.001]、无进展生存期（PFI）（HR =1.99，95% CI：1.60 - 2.46；P<0.001）和疾病特异性生存期（DSS）（HR =2.84，95% CI：2.18 - 3.71；P<0.001）。多变量回归分析证实PCGF1表达是OS的独立预后因素（HR =1.581，95% CI：1.161 - 2.153；P =0.004）。基于功能富集分析，我们鉴定了与PCGF1相关的差异表达基因（DEGs），并发现PCGF1参与调节许多致癌信号通路，如磷脂酰肌醇3激酶和蛋白激酶B通路、Janus激酶/信号转导子和转录激活子（JKT - STAT）信号通路、Notch信号通路和整合素信号通路。此外，我们发现PCGF1表达与Th2细胞丰度呈正相关，但与滤泡辅助性T细胞、中央记忆性T细胞和γδT细胞呈负相关。此外，PCGF1参与了胶质瘤中许多免疫相关过程的调节。
PCGF1是一种有前景的预后生物标志物，由于它控制癌症相关通路和肿瘤免疫，因此在胶质瘤发展中起重要作用。
