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Open Access 01-12-2023 | Metastasis | Research

A pan-cancer analysis revealing the role of LFNG, MFNG and RFNG in tumor prognosis and microenvironment

Authors: Xun Gong, Chenglong Zheng, Haiying Jia, Yangruiyu Liu, Rui Yang, Zizhou Chen, Yihang Pan, Xiaowu Li, Yuchen Liu

Published in: BMC Cancer | Issue 1/2023

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Title: A pan-cancer analysis revealing the role of LFNG, MFNG and RFNG in tumor prognosis and microenvironment
Authors: Xun Gong
Chenglong Zheng
Haiying Jia
Yangruiyu Liu
Rui Yang
Zizhou Chen
Yihang Pan
Xiaowu Li
Yuchen Liu
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Metastasis
Choroidal Melanoma
Pancreatic Cancer
Pancreatic Cancer
Published in: BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-023-11545-3

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Abstract

Background

Methods

Results

Conclusions

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