Identifying potential biomarkers for the diagnosis and treatment of IgA nephropathy based on bioinformatics analysis

BMC Medical Genomics · 11 authors, 1 centre

AI SUMMARY

FIDELITY 100%

POPULATION80 IgAN samples and 27 normal samples from 3 GEO microarray datasets, with in vitro validation in HMC cells

INTERVENTIONBioinformatics analysis of differentially expressed genes, hub gene identification, immune infiltration analysis, and drug prediction; TYROBP expression validated via western blot in a cell model of IgAN

COMPARISONIgAN samples versus normal/healthy control samples

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AGENT 01 · STRUCTURED SUMMARY

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TL;DR

This bioinformatics study analyzed three GEO microarray datasets comprising 80 IgA nephropathy (IgAN) samples and 27 normal samples to identify differentially expressed genes and hub genes as potential diagnostic biomarkers and therapeutic targets. The study identified 10 hub genes including TYROBP, which was validated in an IgAN cell model and showed strong diagnostic specificity for IgAN.

Full summary

1,029 CHARS

This study integrated three GEO microarray datasets containing 80 IgAN and 27 normal kidney samples to identify differentially expressed genes (DEGs) and hub genes for IgAN diagnosis and therapy. A total of 113 DEGs were identified using the limma package, enriched in peptidase regulator activity, cytokine production, and collagen-containing extracellular matrix. Ten hub genes were mined from the PPI network, including TYROBP, FN1, ALB, PLG, IGF1, EGF, HRG, KNG1, CSF1R, and ITGB2. Immune infiltration analysis via CIBERSORT linked several hub genes to infiltrating immune cells. ROC curve analysis indicated that all hub genes exhibited diagnostic value, with TYROBP showing the most promising performance. TYROBP expression was validated in an HMC cell model of IgAN and confirmed to be highly expressed with high diagnostic specificity. Limitations include the absence of clinical validation cohorts, reliance on publicly available microarray data, and CIBERSORT's systematic estimation bias for certain immune cell types.

PICO

PPOPULATION

80 IgAN samples and 27 normal samples from 3 GEO microarray datasets, with in vitro validation in HMC cells

IINTERVENTION

Bioinformatics analysis of differentially expressed genes, hub gene identification, immune infiltration analysis, and drug prediction; TYROBP expression validated via western blot in a cell model of IgAN

OOUTCOME

Diagnostic biomarker identification and therapeutic drug prediction for IgAN

STUDY TYPE

other

SPECIALTY

nephrology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10044383

Identifying potential biomarkers for the diagnosis and treatment of IgA nephropathy based on bioinformatics analysis

BMC Medical Genomics

READ THE FULL PAPER

ABSTRACT

Background IgA nephropathy (IgAN) has become the leading cause of end-stage renal disease in young adults. Nevertheless, the current diagnosis exclusively relies on invasive renal biopsy, and specific treatment is deficient. Thus, our study aims to identify potential crucial genes, thereby providing novel biomarkers for the diagnosis and therapy of IgAN. Methods Three microarray datasets were downloaded from GEO official website. Differentially expressed genes (DEGs) were identified by limma package. GO and KEGG analysis were conducted. Tissue/organ-specific DEGs were distinguished via BioGPS. GSEA was utilized to elucidate the predominant enrichment pathways. The PPI network of DEGs was established, and hub genes were mined through Cytoscape. The CTD database was employed to determine the association between hub genes and IgAN. Infiltrating immune cells and their relationship to hub genes were evaluated based on CIBERSORT. Furthermore, the diagnostic effectiveness of hub markers was subsequently predicted using the ROC curves. The CMap database was applied to investigate potential therapeutic drugs. The expression level and diagnostic accuracy of TYROBP was validated in the cell model of IgAN and different renal pathologies. Results A total of 113 DEGs were screened, which were mostly enriched in peptidase regulator activity, regulation of cytokine production, and collagen-containing extracellular matrix. Among these DEGs, 67 genes manifested pronounced tissue and organ specificity. GSEA analysis revealed that the most significant enriched gene sets were involved in proteasome pathway. Ten hub genes (KNG1, FN1, ALB, PLG, IGF1, EGF, HRG, TYROBP, CSF1R, and ITGB2) were recognized. CTD showed a close connection between ALB, IGF, FN1 and IgAN. Immune infiltration analysis elucidated that IGF1, EGF, HRG, FN1, ITGB2, and TYROBP were closely associated with infiltrating immune cells. ROC curves reflected that all hub genes, especially TYROBP, exhibited a good diagnostic value for IgAN. Verteporfin, moxonidine, and procaine were the most significant three therapeutic drugs. Further exploration proved that TYROBP was not only highly expressed in IgAN, but exhibited high specificity for the diagnosis of IgAN. Conclusions This study may offer novel insights into the mechanisms involved in IgAN occurrence and progression and the selection of diagnostic markers and therapeutic targets for IgAN. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-023-01494-y.

CITATION EXPORT

Xiaohui Li, Mengru Zeng, Jialu Liu et al.. Identifying potential biomarkers for the diagnosis and treatment of IgA nephropathy based on bioinformatics analysis. BMC Medical Genomics. (2023). https://doi.org/10.1186/s12920-023-01494-y

AUTHORS

11 · 1 CENTRES

Xiaohui Li, Mengru Zeng, Jialu Liu, Shumin Zhang, Yifei Liu, Yuee Zhao, Cong Wei, Kexin Yang, Ying Huang, Lei Zhang, Li Xiao

grid.216417.70000 0001 0379 7164Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital, Central South University, Changsha, 410011 China