# Identification of key genes related to lymphangiogenesis in venous thromboembolism through transcriptomics and verification by RT-qPCR

## TL;DR

This study identifies MYC and NTAN1 as key genes involved in lymphangiogenesis and immune-metabolic dysregulation in venous thromboembolism, offering new insights into potential therapies.

## Contribution

The study identifies MYC and NTAN1 as pivotal genes linking thrombosis and immune dysregulation in VTE through transcriptomics and RT-qPCR validation.

## Key findings

- MYC and NTAN1 were prioritized as key genes associated with VTE through transcriptomic analysis and RT-qPCR validation.
- Functional analysis showed MYC and NTAN1 are enriched in spliceosome, oxidative phosphorylation, and immune-related pathways.
- MYC was identified as a hub regulated by hsa-miR-449c-5p and JUN, with cisplatin and olaparib suggested as potential therapies.

## Abstract

Venous thromboembolism (VTE), a life-threatening cardiovascular disorder, involves complex interactions between thrombosis and immune dysregulation. Lymphangiogenesis-related genes (LRGs) may directly induce thrombosis by regulating endothelial function, the coagulation cascade, or inflammatory signaling pathways. This research was intended to uncover LRG-associated key genes and elucidate their molecular mechanisms in VTE.

Transcriptomic datasets from public databases were analyzed to identify differentially expressed genes (DEGs) between VTE and control samples. Subsequently, candidate genes were screened by overlapping the DEGs with LRGs obtained from the literature. Functional analysis was then performed on candidate genes. Machine learning algorithms and expression validation were employed to refine key genes. Moreover, gene set enrichment analysis (GSEA), immune infiltration, and regulatory and disease-gene-drug network analyses were performed. Finally, key genes’ expression levels were validated via real-time quantitative polymerase chain reaction (RT-qPCR).

To sum up, 810 DEGs were identified, of which 30 DEGs were selected as candidate genes. Machine learning and expression validation prioritized MYC and NTAN1 as key genes. Functional analysis revealed their enrichment in spliceosome, oxidative phosphorylation, and immune-related pathways. MYC and NTAN1 correlated with regulatory T cells and M2 macrophages. Furthermore, the microRNA (miRNA)-mRNA-transcription factor (TF) network identified MYC as a hub regulated by hsa-miR-449c-5p and JUN. Disease-gene-drug network highlighted cisplatin and olaparib as potential MYC-targeted therapy. RT-qPCR confirmed MYC downregulation and NTAN1 upregulation in VTE (p < 0.05), consistent with the bioinformatics results.

This study identified MYC and NTAN1 as pivotal regulators of VTE, bridging thrombotic progression with immune-metabolic dysregulation. The findings provided novel insights into key genes and immunomodulatory therapies for VTE.