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Integrated Bioinformatics and Validation Reveal IFI27 and Its Related Molecules as Potential Identifying Genes in
Zhiyu Xiong1, Ping Chen1, Mengqin Yuan1
1Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Abstract:
Liver cirrhosis remains a significant global public health concern, with liver transplantation standing as the foremost effective treatment currently available. Therefore, investigating the pathogenesis of liver cirrhosis and developing novel therapies is imperative. Mitochondrial dysfunction stands out as a pivotal factor in its development. This study aimed to elucidate the relationship between mitochondria dysfunction and liver cirrhosis using bioinformatic methods to unveil its pathogenesis. Initially, we identified 460 co-expressed differential genes (co-DEGs) from the GSE14323 and GSE25097 datasets, alongside their combined datasets. Functional analysis revealed that these co-DEGs were associated with inflammatory cytokines and cirrhosis-related signaling pathways. Utilizing weighted gene co-expression network analysis (WCGNA), we screened module genes, intersecting them with co-DEGs and oxidative stress-related mitochondrial genes. Two algorithms (least absolute shrinkage and selection operator (LASSO) regression and SVE-RFE) were then employed to further analyze the intersecting genes. Finally, COX7A1 and IFI27 emerged as identifying genes for liver cirrhosis, validated through a receiver operating characteristic (ROC) curve analysis and related experiments. Additionally, immune infiltration highlighted a strong correlation between macrophages and cirrhosis, with the identifying genes (COX7A1 and IFI27) being significantly associated with macrophages. In conclusion, our findings underscore the critical role of oxidative stress-related mitochondrial genes (COX7A1 and IFI27) in liver cirrhosis development, highlighting their association with macrophage infiltration. This study provides novel insights into understanding the pathogenesis of liver cirrhosis.
Insights
Mitochondrial dysfunction drives liver cirrhosis. This study identifies COX7A1 and IFI27 as key genes linked to macrophage infiltration, offering new therapeutic targets for liver cirrhosis.
Area of Science:
- Hepatology
- Mitochondrial Biology
- Bioinformatics
Background:
- Liver cirrhosis is a major global health issue.
- Mitochondrial dysfunction is a key factor in liver cirrhosis pathogenesis.
- Effective treatments for liver cirrhosis are limited, necessitating research into its causes.
Purpose of the Study:
- To investigate the link between mitochondrial dysfunction and liver cirrhosis using bioinformatics.
- To identify novel biomarkers and therapeutic targets for liver cirrhosis.
Main Methods:
- Differential gene expression analysis of GSE14323 and GSE25097 datasets.
- Weighted gene co-expression network analysis (WCGNA).
- LASSO regression and SVE-RFE algorithms for gene selection and validation via ROC curve analysis.
Main Results:
- Identified 460 co-expressed differential genes (co-DEGs) linked to inflammation and cirrhosis pathways.
- Screened and identified COX7A1 and IFI27 as key genes associated with liver cirrhosis.
- Found a significant correlation between macrophage infiltration and liver cirrhosis, with COX7A1 and IFI27 associated with macrophages.
Conclusions:
- COX7A1 and IFI27 are critical oxidative stress-related mitochondrial genes in liver cirrhosis development.
- These genes are associated with macrophage infiltration, providing insights into cirrhosis pathogenesis.
- The study offers novel biomarkers and potential therapeutic targets for liver cirrhosis.
