Fibroblast Activation Protein-Alpha is a Prognostic Biomarker Associated With Ferroptosis in Stomach Adenocarcinoma

Background: The potential role of fibroblast activation protein-alpha (FAP) in modulating the progression and invasion of stomach adenocarcinoma (STAD) has not yet been comprehensively investigated. This study aimed to explore the role of FAP in STAD and the underlying association between FAP and th...

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Main Authors: Zejian Lyu, Yafang Li, Dandan Zhu, Sifan Wu, Fei Hu, Yu Zhang, Yong Li, Tieying Hou
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-03-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.859999/full
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author Zejian Lyu
Zejian Lyu
Yafang Li
Yafang Li
Dandan Zhu
Sifan Wu
Sifan Wu
Fei Hu
Fei Hu
Yu Zhang
Yong Li
Yong Li
Tieying Hou
Tieying Hou
Tieying Hou
Tieying Hou
Tieying Hou
author_facet Zejian Lyu
Zejian Lyu
Yafang Li
Yafang Li
Dandan Zhu
Sifan Wu
Sifan Wu
Fei Hu
Fei Hu
Yu Zhang
Yong Li
Yong Li
Tieying Hou
Tieying Hou
Tieying Hou
Tieying Hou
Tieying Hou
author_sort Zejian Lyu
collection DOAJ
description Background: The potential role of fibroblast activation protein-alpha (FAP) in modulating the progression and invasion of stomach adenocarcinoma (STAD) has not yet been comprehensively investigated. This study aimed to explore the role of FAP in STAD and the underlying association between FAP and the tumor microenvironment (TME) and ferroptosis.Methods: Overall survival was analyzed to evaluate the prognostic value of FAP based on gene expression data and clinical information on STAD. Associations between FAP expression, clinical parameters, and immune characteristics were comprehensively analyzed. The ferroptosis-related patterns of STAD samples were investigated based on 43 ferroptosis-related genes, and the correlations between these clusters and clinical characteristics were evaluated. The possible biological functions and pathways were explored using gene set enrichment analysis (GSEA).Results: FAP was identified as a novel biomarker that significantly contributed to the poor prognosis of STAD (hazard ratio = 1.270, P = 0.013). The elevated level of FAP expression was related to a more advanced tumor stage in STAD. The close relationship between FAP and the TME was validated. Four distinct ferroptosis-related clusters (A–D) were evident. Evaluating ferroptosis-related clusters could illustrate the stages of STAD and patient prognosis. Cluster C displayed the lowest FAP expression and a better prognosis than the other clusters. The different clusters were linked to different biological mechanisms, including epithelial-mesenchymal transition and immune-relevant pathways.Conclusion: FAP is a promising biomarker to distinguish prognosis and is associated with the TME and ferroptosis in STAD.
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spelling doaj.art-e7bd1befbec34c1e91a25d72504058922022-12-22T01:12:06ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-03-011010.3389/fcell.2022.859999859999Fibroblast Activation Protein-Alpha is a Prognostic Biomarker Associated With Ferroptosis in Stomach AdenocarcinomaZejian Lyu0Zejian Lyu1Yafang Li2Yafang Li3Dandan Zhu4Sifan Wu5Sifan Wu6Fei Hu7Fei Hu8Yu Zhang9Yong Li10Yong Li11Tieying Hou12Tieying Hou13Tieying Hou14Tieying Hou15Tieying Hou16The Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaGuangdong Clinical Laboratory Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Clinical Laboratory Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Clinical Laboratory Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaGuangdong Clinical Laboratory Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe First School of Clinical Medicine, Guangdong Medical University, Zhanjiang, ChinaMedical Department, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaGuangdong Clinical Laboratory Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaGuangdong Clinical Laboratory Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaThe First School of Clinical Medicine, Guangdong Medical University, Zhanjiang, ChinaMedical Department, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaBackground: The potential role of fibroblast activation protein-alpha (FAP) in modulating the progression and invasion of stomach adenocarcinoma (STAD) has not yet been comprehensively investigated. This study aimed to explore the role of FAP in STAD and the underlying association between FAP and the tumor microenvironment (TME) and ferroptosis.Methods: Overall survival was analyzed to evaluate the prognostic value of FAP based on gene expression data and clinical information on STAD. Associations between FAP expression, clinical parameters, and immune characteristics were comprehensively analyzed. The ferroptosis-related patterns of STAD samples were investigated based on 43 ferroptosis-related genes, and the correlations between these clusters and clinical characteristics were evaluated. The possible biological functions and pathways were explored using gene set enrichment analysis (GSEA).Results: FAP was identified as a novel biomarker that significantly contributed to the poor prognosis of STAD (hazard ratio = 1.270, P = 0.013). The elevated level of FAP expression was related to a more advanced tumor stage in STAD. The close relationship between FAP and the TME was validated. Four distinct ferroptosis-related clusters (A–D) were evident. Evaluating ferroptosis-related clusters could illustrate the stages of STAD and patient prognosis. Cluster C displayed the lowest FAP expression and a better prognosis than the other clusters. The different clusters were linked to different biological mechanisms, including epithelial-mesenchymal transition and immune-relevant pathways.Conclusion: FAP is a promising biomarker to distinguish prognosis and is associated with the TME and ferroptosis in STAD.https://www.frontiersin.org/articles/10.3389/fcell.2022.859999/fullFAPstomach adenocarcinomatumor microenvironmentferroptosisbiomarker
spellingShingle Zejian Lyu
Zejian Lyu
Yafang Li
Yafang Li
Dandan Zhu
Sifan Wu
Sifan Wu
Fei Hu
Fei Hu
Yu Zhang
Yong Li
Yong Li
Tieying Hou
Tieying Hou
Tieying Hou
Tieying Hou
Tieying Hou
Fibroblast Activation Protein-Alpha is a Prognostic Biomarker Associated With Ferroptosis in Stomach Adenocarcinoma
Frontiers in Cell and Developmental Biology
FAP
stomach adenocarcinoma
tumor microenvironment
ferroptosis
biomarker
title Fibroblast Activation Protein-Alpha is a Prognostic Biomarker Associated With Ferroptosis in Stomach Adenocarcinoma
title_full Fibroblast Activation Protein-Alpha is a Prognostic Biomarker Associated With Ferroptosis in Stomach Adenocarcinoma
title_fullStr Fibroblast Activation Protein-Alpha is a Prognostic Biomarker Associated With Ferroptosis in Stomach Adenocarcinoma
title_full_unstemmed Fibroblast Activation Protein-Alpha is a Prognostic Biomarker Associated With Ferroptosis in Stomach Adenocarcinoma
title_short Fibroblast Activation Protein-Alpha is a Prognostic Biomarker Associated With Ferroptosis in Stomach Adenocarcinoma
title_sort fibroblast activation protein alpha is a prognostic biomarker associated with ferroptosis in stomach adenocarcinoma
topic FAP
stomach adenocarcinoma
tumor microenvironment
ferroptosis
biomarker
url https://www.frontiersin.org/articles/10.3389/fcell.2022.859999/full
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