Comprehensive analysis of ferroptosis patterns and immunologic characteristics in antineutrophil cytoplasmic antibody-associated vasculitis
Objective To lay the groundwork for formulating novel immunotherapies through understanding the regulatory role of ferroptosis and its function in immune microenvironment in ANCA-associated vasculitis (AAV) with renal injury. Methods Kidney data sets on AAV were downloaded from the database of Gene...
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| Format: | Article |
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Editorial Department of Journal of Clinical Nephrology
2023-11-01
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| Series: | Linchuang shenzangbing zazhi |
| Subjects: | |
| Online Access: | http://www.lcszb.com/cn/article/doi/10.3969/j.issn.1671-2390.2023.11.007 |
| _version_ | 1797299545787334656 |
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| author | Mi Tao Ming-hui Geng Yu-yan Li Yi-qing He Wen-wen Liao Xiao-yan Wu Ping Gao |
| author_facet | Mi Tao Ming-hui Geng Yu-yan Li Yi-qing He Wen-wen Liao Xiao-yan Wu Ping Gao |
| author_sort | Mi Tao |
| collection | DOAJ |
| description | Objective To lay the groundwork for formulating novel immunotherapies through understanding the regulatory role of ferroptosis and its function in immune microenvironment in ANCA-associated vasculitis (AAV) with renal injury. Methods Kidney data sets on AAV were downloaded from the database of Gene Expression Omnibus (GEO). Based upon the results of differential expression, consensus clustering algorithm was employed for identifying the subtypes of iron mortality. Single sample gene set enrichment analysis (ssGSEA) and gene set variation analysis (GSVA) were performed for evaluating the immune invasion and signaling pathways of subtypes. Key ferroptosis-related genes (FRGs) were further screened by LASSO and SVM-RFE algorithms and verified by independent data sets. CIBERSORT was utilized for assessing the abundance of infiltrating immune cells for FRGs. Finally a clinical diagnostic model of FRGs was constructed by rsm package. And the correlation between FRGs and renal function was examined by Nephroseq V5 database. Results Twenty-four ferroptosis related genes were significantly differentially expressed in AAV with kidney injury. Unsupervised cluster analysis revealed the regulatory patterns of two different ferroptosis subtypes with significant differences in gene expression, immune infiltration and biological functional pathways. A set of FRGs composed of ALOX5, CD44, CRYAB, TP53, and FTH1 was selected by two machine learning algorithms. It could effectively distinguish AAV with kidney injury from normal control group. CCR, macrophage and HLA were correlated positively with FRGs. Area under ROC curve of clinical diagnostic model constructed by FRGs was 0. 961. FRGs were correlated negatively with glomerular filtration rate (GFR). However, except for CRYAB and FTH1, other FRGs were correlated positively with serum creatinine (Scr). It implicated their potential relevance to renal injury in ANCA-associated vasculitis (AAV) and their potential as prognostic biomarkers. Conclusions Ferroptosis in AAV with kidney injury is correlated closely with immune microenvironment. It provides rationales for devising new treatments for AAV with kidney injury through a better understanding the pattern of ferroptosis. |
| first_indexed | 2024-03-07T22:51:27Z |
| format | Article |
| id | doaj.art-746c2e6b044d494da4387c309e47e3cb |
| institution | Directory Open Access Journal |
| issn | 1671-2390 |
| language | zho |
| last_indexed | 2024-03-07T22:51:27Z |
| publishDate | 2023-11-01 |
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| series | Linchuang shenzangbing zazhi |
| spelling | doaj.art-746c2e6b044d494da4387c309e47e3cb2024-02-23T09:28:23ZzhoEditorial Department of Journal of Clinical NephrologyLinchuang shenzangbing zazhi1671-23902023-11-01231192193110.3969/j.issn.1671-2390.2023.11.00720230004Comprehensive analysis of ferroptosis patterns and immunologic characteristics in antineutrophil cytoplasmic antibody-associated vasculitisMi Tao0Ming-hui Geng1Yu-yan Li2Yi-qing He3Wen-wen Liao4Xiao-yan Wu5Ping Gao6Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071，ChinaDepartment of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071，ChinaDepartment of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071，ChinaDepartment of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071，ChinaDepartment of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071，ChinaDepartment of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071，ChinaDepartment of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071，ChinaObjective To lay the groundwork for formulating novel immunotherapies through understanding the regulatory role of ferroptosis and its function in immune microenvironment in ANCA-associated vasculitis (AAV) with renal injury. Methods Kidney data sets on AAV were downloaded from the database of Gene Expression Omnibus (GEO). Based upon the results of differential expression, consensus clustering algorithm was employed for identifying the subtypes of iron mortality. Single sample gene set enrichment analysis (ssGSEA) and gene set variation analysis (GSVA) were performed for evaluating the immune invasion and signaling pathways of subtypes. Key ferroptosis-related genes (FRGs) were further screened by LASSO and SVM-RFE algorithms and verified by independent data sets. CIBERSORT was utilized for assessing the abundance of infiltrating immune cells for FRGs. Finally a clinical diagnostic model of FRGs was constructed by rsm package. And the correlation between FRGs and renal function was examined by Nephroseq V5 database. Results Twenty-four ferroptosis related genes were significantly differentially expressed in AAV with kidney injury. Unsupervised cluster analysis revealed the regulatory patterns of two different ferroptosis subtypes with significant differences in gene expression, immune infiltration and biological functional pathways. A set of FRGs composed of ALOX5, CD44, CRYAB, TP53, and FTH1 was selected by two machine learning algorithms. It could effectively distinguish AAV with kidney injury from normal control group. CCR, macrophage and HLA were correlated positively with FRGs. Area under ROC curve of clinical diagnostic model constructed by FRGs was 0. 961. FRGs were correlated negatively with glomerular filtration rate (GFR). However, except for CRYAB and FTH1, other FRGs were correlated positively with serum creatinine (Scr). It implicated their potential relevance to renal injury in ANCA-associated vasculitis (AAV) and their potential as prognostic biomarkers. Conclusions Ferroptosis in AAV with kidney injury is correlated closely with immune microenvironment. It provides rationales for devising new treatments for AAV with kidney injury through a better understanding the pattern of ferroptosis.http://www.lcszb.com/cn/article/doi/10.3969/j.issn.1671-2390.2023.11.007anti-neutrophil cytoplasmic antibody-associated vasculitiskidney injuryferroptosisimmune characteristicscomputational biology |
| spellingShingle | Mi Tao Ming-hui Geng Yu-yan Li Yi-qing He Wen-wen Liao Xiao-yan Wu Ping Gao Comprehensive analysis of ferroptosis patterns and immunologic characteristics in antineutrophil cytoplasmic antibody-associated vasculitis Linchuang shenzangbing zazhi anti-neutrophil cytoplasmic antibody-associated vasculitis kidney injury ferroptosis immune characteristics computational biology |
| title | Comprehensive analysis of ferroptosis patterns and immunologic characteristics in antineutrophil cytoplasmic antibody-associated vasculitis |
| title_full | Comprehensive analysis of ferroptosis patterns and immunologic characteristics in antineutrophil cytoplasmic antibody-associated vasculitis |
| title_fullStr | Comprehensive analysis of ferroptosis patterns and immunologic characteristics in antineutrophil cytoplasmic antibody-associated vasculitis |
| title_full_unstemmed | Comprehensive analysis of ferroptosis patterns and immunologic characteristics in antineutrophil cytoplasmic antibody-associated vasculitis |
| title_short | Comprehensive analysis of ferroptosis patterns and immunologic characteristics in antineutrophil cytoplasmic antibody-associated vasculitis |
| title_sort | comprehensive analysis of ferroptosis patterns and immunologic characteristics in antineutrophil cytoplasmic antibody associated vasculitis |
| topic | anti-neutrophil cytoplasmic antibody-associated vasculitis kidney injury ferroptosis immune characteristics computational biology |
| url | http://www.lcszb.com/cn/article/doi/10.3969/j.issn.1671-2390.2023.11.007 |
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