Fringe是一种糖基转移酶，参与肿瘤的发生和转移。然而，目前缺乏对Fringe家族成员疯狂边缘（LFNG）、躁狂边缘（MFNG）、激进边缘（RFNG）在人类癌症中的全面分析。在这项研究中，我们对33个Fringe家族成员进行了泛癌分析。癌症类型以及来自癌症基因组图谱 (TCGA) 项目的转录组、基因组、甲基化数据。通过使用多个数据库（例如cBioPortal、Human Protein Atlas、GeneCards、STRING、MSigDB）研究Fringe家族成员表达与患者总生存率、拷贝数变异、甲基化、基因本体富集和肿瘤浸润淋巴细胞（TIL）之间的相关性、TISIDB 和 TIMER2。进行体外实验和免疫组织化学测定来验证我们的发现。LFNG、MFNG、RFNG 的高表达水平与多种癌症的总体生存率较差密切相关，特别是在胰腺腺癌 (PAAD)、葡萄膜黑色素瘤 (UVM) 和脑低级神经胶质瘤（LGG）。拷贝数变异分析显示，LFNG 的二倍体和增益突变在 PAAD 和胃腺癌 (STAD) 中显着增加，并且与启动子区域的甲基化水平显着相关。这些Fringe家族成员的高表达组和低表达组之间的显着差异基因被发现在免疫反应和T细胞激活途径、细胞外基质粘附途径、RNA剪接和离子转运途径中一致富集。肿瘤浸润淋巴细胞 (TIL) 丰度与 LFNG、MFNG 和 RFNG 表达之间的相关性表明，高 LFNG 表达与较低的 TIL 水平相关，特别是在 PAAD 中。利用胰腺癌PANC1细胞进行的体外实验表明，LFNG过表达促进细胞增殖和侵袭。免疫组织化学检测90例PAAD患者验证了LFNG的表达水平及其与预后的关系。我们的研究为LFNG、MFNG和RFNG的表达、突变、拷贝数、启动子甲基化水平变化以及预后价值提供了相对全面的了解在不同的肿瘤中。高 LFNG 表达可能作为 PAAD 的不良预后分子标志物。© 2023。作者。

Fringe is a glycosyltransferase involved in tumor occurrence and metastasis. However, a comprehensive analysis of the Fringe family members lunatic fringe (LFNG), manic fringe (MFNG), radical fringe (RFNG) in human cancers is lacking.In this study, we performed a pan-cancer analysis of Fringe family members in 33 cancer types with transcriptomic, genomic, methylation data from The Cancer Genome Atlas (TCGA) project. The correlation between Fringe family member expression and patient overall survival, copy number variation, methylation, Gene Ontology enrichment, and tumor-infiltrating lymphocytes (TILs) was investigated by using multiple databases, such as cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2. In vitro experiments and immunohistochemical assays were performed to validate our findings.High expression levels of LFNG, MFNG, RFNG were closely associated with poor overall survival in multiple cancers, particularly in pancreatic adenocarcinoma (PAAD), uveal melanoma (UVM), and brain lower-grade glioma (LGG). Copy number variation analysis revealed that diploid and gain mutations of LFNG was significantly increased in PAAD and stomach adenocarcinoma (STAD), and significantly associated with the methylation levels in promoter regions. Significant differential genes between high and low expression groups of these Fringe family members were found to be consistently enriched in immune response and T cell activation pathway, extracellular matrix adhesion pathway, RNA splicing and ion transport pathways. Correlation between the abundance of tumor-infiltrating lymphocytes (TILs) and LFNG, MFNG, and RFNG expression showed that high LFNG expression was associated with lower TIL levels, particularly in PAAD. In vitro experiment by using pancreatic cancer PANC1 cells showed that LFNG overexpression promoted cell proliferation and invasion. Immunohistochemical assay in 90 PAAD patients verified the expression level of LFNG and its relationship with the prognosis.Our study provides a relatively comprehensive understanding of the expression, mutation, copy number, promoter methylation level changes along with prognosis values of LFNG, MFNG, and RFNG in different tumors. High LFNG expression may serve as a poor prognosis molecular marker for PAAD.© 2023. The Author(s).