Background: Lung squamous cell carcinoma (LUSC) is a subtypes of non-small cell lung cancer (NSCLC). It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway. Protocadherin-gamma subfamily B4 (PCDHGB4) as a family member in LUSC was rarely reported. The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC using bioinformatics methods.
Methods: The Cancer Genome Atlas (TCGA), cBioPortal and UALCAN databases were used to analyze the expression, prognosis, clinicopathological features, immune cell infiltration, immune regulatory genes, immune checkpoint inhibitors (ICIs), and methyltransferases of PCDHGB4 in LUSC. At the single cell level, we analyzed the clustering results of cell subtypes and the expression of PCDHGB4 in different immune cell subpopulations. In addition, we compared the promoter methylation levels of PCDHGB4 in LUSC tissues and normal tissues and performed protein-protein interaction and mutation analysis. Finally, enrichment analysis was performed based on the differentially expressed genes.
Results: Bioinformatics analysis results showed that the expression level of PCDHGB4 in LUSC tissues was lower than that in normal tissues. Survival analysis showed that increased PCDHGB4 expression was associated with poor prognosis. Single-cell sequencing analysis showed that PCDHGB4 was expressed in T cells, monocytes or macrophages, and dendritic cells. It was further found that PCDHGB4 played an important role in tumor immunity and confirmed that PCDHGB4 was associated with immune checkpoints, immune regulatory genes, and methyltransferases. Besides, enrichment analysis revealed that PCDHGB4 was involved in multiple cancer-related pathways.
Conclusions: The expression of PCDHGB4 was low in LUSC. PCDHGB4 was related to the poor prognosis of patients, and PCDHGB4 was closely related to the infiltration and pathway of tumor immune cells. PCDHGB4 may be a potential prognostic marker and a new target for immunotherapy in LUSC.
【中文题目：基于生物信息学分析探索PCDHGB4 在肺鳞癌发生中的作用】 【中文摘要：背景与目的 肺鳞状细胞癌（lung squamous cell carcinoma, LUSC）是非小细胞肺癌（non-small cell lung cancer, NSCLC）的亚型之一。有报道原钙黏蛋白γ家族的成员能通过抑制Wnt信号通路来调节肿瘤细胞的生长，原钙黏蛋白γB4（protocadherin-gamma subfamily B4, PCDHGB4）作为家族成员在LUSC中的研究少有报道，本研究旨在通过生物信息学方法探究PCDHGB4在LUSC发生发展中的作用及潜在的预后价值。方法 应用癌症基因组图谱（The Cancer Genome Atlas, TCGA）、cBioPortal和UALCAN等数据库，对PCDHGB4在LUSC中的表达与预后、临床病理特征、免疫细胞浸润、免疫调节基因、免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）和甲基转移酶等进行分析。单细胞水平的研究对细胞亚型的聚类结果和PCDHGB4在不同免疫细胞亚群中的表达情况进行了分析。此外，我们还比较了LUSC组织与正常组织中PCDHGB4的启动子甲基化水平，并对其进行了蛋白质-蛋白质相互作用和突变分析。最后基于差异表达基因进行富集分析。结果 生信分析结果显示PCDHGB4在LUSC组织的表达水平低于正常组织。生存分析显示，PCDHGB4表达增加与患者较差的预后有关。单细胞分析显示，PCDHGB4主要在T细胞、单核细胞或巨噬细胞以及树突状细胞中表达，进一步发现PCDHGB4在肿瘤免疫中发挥着不可忽视的作用，并证实了PCDHGB4与免疫检查点途径基因、免疫调节基因和甲基转移酶有一定的相关性。此外，通过富集分析发现PCDHGB4参与了癌症相关的多条通路。结论 PCDHGB4在LUSC中低表达，PCDHGB4与患者预后不良有关，并且PCDHGB4与肿瘤免疫细胞浸润和通路密切相关。PCDHGB4可能是LUSC潜在的预后标志物和免疫治疗新靶点。 】 【中文关键词：PCDHGB4；肺肿瘤；预后】.
Keywords: Lung neoplasms; PCDHGB4; Prognosis.