Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer

Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease. Its high disability rate has a serious impact on society and individuals, but there is still a lack of effective and reliable diagnostic markers and therapeutic targets for RA. In this study, we integrated RA patient informati...

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Main Authors: ZhenYu Zhao, ShaoJie He, XinCheng Yu, XiaoFeng Lai, Sheng Tang, El Akkawi Mariya M., MoHan Wang, Hai Yan, XingQi Huang, Shan Zeng, DingSheng Zha
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.954848/full
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author ZhenYu Zhao
ShaoJie He
XinCheng Yu
XiaoFeng Lai
Sheng Tang
El Akkawi Mariya M.
MoHan Wang
Hai Yan
XingQi Huang
Shan Zeng
DingSheng Zha
author_facet ZhenYu Zhao
ShaoJie He
XinCheng Yu
XiaoFeng Lai
Sheng Tang
El Akkawi Mariya M.
MoHan Wang
Hai Yan
XingQi Huang
Shan Zeng
DingSheng Zha
author_sort ZhenYu Zhao
collection DOAJ
description Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease. Its high disability rate has a serious impact on society and individuals, but there is still a lack of effective and reliable diagnostic markers and therapeutic targets for RA. In this study, we integrated RA patient information from three GEO databases for differential gene expression analysis. Additionally, we also obtained pan-cancer-related genes from the TCGA and GTEx databases. For RA-related differential genes, we performed functional enrichment analysis and constructed a weighted gene co-expression network (WGCNA). Then, we obtained 490 key genes by intersecting the significant module genes selected by WGCNA and the differential genes. After using the RanddomForest, SVM-REF, and LASSO three algorithms to analyze these key genes and take the intersection, based on the four core genes (BTN3A2, CYFIP2, ST8SIA1, and TYMS) that we found, we constructed an RA diagnosis. The nomogram model showed good reliability and validity after evaluation, and the ROC curves of the four genes showed that these four genes played an important role in the pathogenesis of RA. After further gene correlation analysis, immune infiltration analysis, and mouse gene expression validation, we finally selected CYFIP2 as the cut-in gene for pan-cancer analysis. The results of the pan-cancer analysis showed that CYFIP2 was closely related to the prognosis of patients with various tumors, the degree of immune cell infiltration, as well as TMB, MSI, and other indicators, suggesting that this gene may be a potential intervention target for human diseases including RA and tumors.
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spelling doaj.art-6f2e0b0575ce4191b369879130d0f88a2022-12-22T01:40:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.954848954848Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-CancerZhenYu Zhao0ShaoJie He1XinCheng Yu2XiaoFeng Lai3Sheng Tang4El Akkawi Mariya M.5MoHan Wang6Hai Yan7XingQi Huang8Shan Zeng9DingSheng Zha10Department of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopaedics, Panyu Hospital of Chinese Medicine, Guangzhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopedics, The Sixth Affiliated Hospital, South China University of Technology, Foshan, ChinaDepartment of Plastic and Reconstructive Surgery, ZhuJiang Hospital of Southern Medical University, GuangZhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Medicine, Flushing Hospital Medical Center, Flushing, NY, United StatesDepartment of Neurosurgery , General Hospital of Tianjin Medical University, ChinaDepartment of Rheumatology, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaRheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease. Its high disability rate has a serious impact on society and individuals, but there is still a lack of effective and reliable diagnostic markers and therapeutic targets for RA. In this study, we integrated RA patient information from three GEO databases for differential gene expression analysis. Additionally, we also obtained pan-cancer-related genes from the TCGA and GTEx databases. For RA-related differential genes, we performed functional enrichment analysis and constructed a weighted gene co-expression network (WGCNA). Then, we obtained 490 key genes by intersecting the significant module genes selected by WGCNA and the differential genes. After using the RanddomForest, SVM-REF, and LASSO three algorithms to analyze these key genes and take the intersection, based on the four core genes (BTN3A2, CYFIP2, ST8SIA1, and TYMS) that we found, we constructed an RA diagnosis. The nomogram model showed good reliability and validity after evaluation, and the ROC curves of the four genes showed that these four genes played an important role in the pathogenesis of RA. After further gene correlation analysis, immune infiltration analysis, and mouse gene expression validation, we finally selected CYFIP2 as the cut-in gene for pan-cancer analysis. The results of the pan-cancer analysis showed that CYFIP2 was closely related to the prognosis of patients with various tumors, the degree of immune cell infiltration, as well as TMB, MSI, and other indicators, suggesting that this gene may be a potential intervention target for human diseases including RA and tumors.https://www.frontiersin.org/articles/10.3389/fimmu.2022.954848/fullrheumatoid arthritisCYFIP2GEOWGCNApan-cancerST8SIA1
spellingShingle ZhenYu Zhao
ShaoJie He
XinCheng Yu
XiaoFeng Lai
Sheng Tang
El Akkawi Mariya M.
MoHan Wang
Hai Yan
XingQi Huang
Shan Zeng
DingSheng Zha
Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer
Frontiers in Immunology
rheumatoid arthritis
CYFIP2
GEO
WGCNA
pan-cancer
ST8SIA1
title Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer
title_full Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer
title_fullStr Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer
title_full_unstemmed Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer
title_short Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer
title_sort analysis and experimental validation of rheumatoid arthritis innate immunity gene cyfip2 and pan cancer
topic rheumatoid arthritis
CYFIP2
GEO
WGCNA
pan-cancer
ST8SIA1
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.954848/full
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