Association of abnormal NDUFB2 and UQCRH expression with venous thromboembolism in patients with liver cirrhosis

Abstract

Venous thromboembolism (VTE) refers to abnormal coagulation of blood in veins, resulting in complete or incomplete occlusion of the blood vessels. Patients with liver cirrhosis are prone to blood clots. However, relationship between NDUFB2 and UQCRH and VTE is not clear. GSE19151 and GSE48000 profiles for venous thromboembolism were downloaded from gene expression omnibus (GEO) generated using GPL571 and GPL10558. Multiple datasets were merged and batched. The differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. The construction and analysis of protein–protein interaction (PPI) network, functional enrichment analysis, Gene Set Enrichment Analysis (GSEA) were conducted. Gene expression heat map was drawn. Comparative toxicogenomics database (CTD) analysis were performed to find disease most related to the core genes. Western blotting (WB) experiments were further verified. TargetScan screened miRNAs that regulated central DEGs. 129 DEGs were identified. According to gene ontology (GO), DEGs were mainly enriched in mRNA metabolism, oxidative phosphorylation, nucleic acid binding and enzyme binding. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis showed that target cells were mainly enriched in ribosomes and oxidative phosphorylation. The intersection of enrichment items and GOKEGG enrichment items of DEGs is mainly enriched in oxidative phosphorylation, myocardial contraction and ribosome. In the metascape enrichment project, dna template transcription, cell stress response regulation and proton transport across the membrane can be seen in the GO enrichment project. The PPI network obtained 10 core genes (COX7C, NDUFB2, ATP5O, NDUFA4, NDUFAB1, ATP5C1, ATP5L, NDUFA7, NDUFA6, UQCRH). Gene expression heat map showed that 5 core genes (NDUFAB1, NDUFB2, UQCRH, COX7C, NDUFA4) were highly expressed in venous thromboembolism samples, and lowly expression in normal tissue samples, and 2 core genes (NDUFA7, NDUFA6) were lowly expressed in venous thromboembolism samples. CTD analysis showed that 5 genes (NDUFAB1, NDUFB2, UQCRH, COX7C, NDUFA4) were found to be associated with obesity, necrosis, inflammation and hepatomegaly. The result of WB showed that expression level of NDUFB2 and UQCR in venous thromboembolism was higher than that in control group. NDUFB2 and UQCRH are highly expressed in venous thromboembolism with liver cirrhosis, making them potential molecular targets for early diagnosis and precise treatment.