# Identification of Key Genes for Alcoholic Hepatitis Using Integrated Network Analysis of Differential lncRNA and Gene Expression

**Authors:** Bihuan Hu, Hui Xia, Peixuan Tian, Xinbao Li, Yu Yang, Zixuan Zhu, Yajie Zhou, Wang Liao, Shoakang Wang, Ligang Yang, Guiju Sun, Jing Sui

PMC · DOI: 10.3390/ijms26136104 · International Journal of Molecular Sciences · 2025-06-25

## TL;DR

This study identifies key genes and lncRNAs involved in alcoholic hepatitis using network analysis, revealing potential biomarkers for diagnosis and treatment.

## Contribution

The novel contribution is the identification of 12 key mRNAs and 14 lncRNAs in an mRNA-lncRNA regulatory network specific to alcoholic hepatitis.

## Key findings

- Differentially expressed genes are linked to lipid metabolism, inflammation, and fibrosis pathways.
- 12 mRNAs and 14 lncRNAs were identified as key players in alcoholic hepatitis development.
- Key genes are concentrated in metabolic and cancer-related signaling pathways.

## Abstract

Alcoholic liver disease (ALD) is a type of liver disease with complex pathogenic factors. In 2019, alcohol caused 11 million life-years to be lost globally, and the mortality rate has continued to rise. This study aims to explore the exclusive gene profile of AH and construct an mRNA-lncRNA regulatory network through an integrative analysis and database validation to reveal potential key biomarkers. We obtained expression data for alcoholic hepatitis from the GEO database; screened differentially expressed genes (DEGs) through a weighted gene co-expression network analysis (WGCNA); conducted a GO&KEGG analysis; and focused on the enrichment pathways for the top 20 genes. Hub genes were selected using cytoHubba and MCODE to construct the mRNA-lncRNA regulatory network, and key genes were confirmed using GSE167308 and GSE28619. We obtained 2552 differentially expressed mRNAs and 555 differentially expressed lncRNAs from three databases. Differentially expressed genes are mainly involved in pathways such as lipid metabolism disorders, complement activation, the activation of cancer-related pathways, the excessive activation of inflammatory immunity, and the initiation of cell adhesion and fibrosis. Based on the hub gene analysis, we screened out 43 key genes. By constructing the key mRNA-lncRNA–pathway network, we identified 12 mRNAs (AQP1, ELOVL7, ITPR3, KRT19, KRT23, LAMC2, MMP7, PROM1, SPINT1, STK39, TNFRSF21, and VTCN1) and 14 lncRNAs that play an important role in the occurrence and development of alcoholic hepatitis. To sum up, this article mainly expounds upon the key genes in the occurrence and development of alcoholic hepatitis. The key genes are mainly concentrated within signaling pathways such as metabolic pathways, fatty acid metabolism, and cancer pathways. Twelve differentially expressed mRNAs in the co-expression network can be used as biomarkers and intervention targets for the diagnosis and treatment of alcoholic hepatitis.

## Linked entities

- **Genes:** AQP1 (aquaporin 1 (Colton blood group)) [NCBI Gene 358], ELOVL7 (ELOVL fatty acid elongase 7) [NCBI Gene 79993], ITPR3 (inositol 1,4,5-trisphosphate receptor type 3) [NCBI Gene 3710], KRT19 (keratin 19) [NCBI Gene 3880], KRT23 (keratin 23) [NCBI Gene 25984], LAMC2 (laminin subunit gamma 2) [NCBI Gene 3918], MMP7 (matrix metallopeptidase 7) [NCBI Gene 4316], PROM1 (prominin 1) [NCBI Gene 8842], SPINT1 (serine peptidase inhibitor, Kunitz type 1) [NCBI Gene 6692], STK39 (serine/threonine kinase 39) [NCBI Gene 27347], TNFRSF21 (TNF receptor superfamily member 21) [NCBI Gene 27242], VTCN1 (V-set domain containing T cell activation inhibitor 1) [NCBI Gene 79679]
- **Diseases:** alcoholic hepatitis (MONDO:0001505), alcoholic liver disease (MONDO:0043693), cancer (MONDO:0004992)

## Full-text entities

- **Genes:** KRT23 (keratin 23) [NCBI Gene 25984] {aka CK23, HAIK1, K23}, ELOVL7 (ELOVL fatty acid elongase 7) [NCBI Gene 79993], SPINT1 (serine peptidase inhibitor, Kunitz type 1) [NCBI Gene 6692] {aka HAI, HAI1, MANSC2}, AQP1 (aquaporin 1 (Colton blood group)) [NCBI Gene 358] {aka AQP-CHIP, CHIP28, CO}, KRT19 (keratin 19) [NCBI Gene 3880] {aka CK19, K19, K1CS}, LAMC2 (laminin subunit gamma 2) [NCBI Gene 3918] {aka B2T, BM600, CSF, EBR2, EBR2A, JEB3A}, ITPR3 (inositol 1,4,5-trisphosphate receptor type 3) [NCBI Gene 3710] {aka CMT1J, IMD132, IMD133, IP3R, IP3R-3, IP3R3}, VTCN1 (V-set domain containing T cell activation inhibitor 1) [NCBI Gene 79679] {aka B7-H4, B7H4, B7S1, B7X, B7h.5, PRO1291}, MMP7 (matrix metallopeptidase 7) [NCBI Gene 4316] {aka MMP-7, MPSL1, PUMP-1}, TNFRSF21 (TNF receptor superfamily member 21) [NCBI Gene 27242] {aka BM-018, CD358, DR6}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}, STK39 (serine/threonine kinase 39) [NCBI Gene 27347] {aka DCHT, SPAK}
- **Diseases:** fibrosis (MESH:D005355), AH (MESH:D007039), ALD (MESH:D008108), inflammatory immunity (MESH:D054019), cancer (MESH:D009369), lipid metabolism disorders (MESH:D052439), Alcoholic Hepatitis (MESH:D006519), liver disease (MESH:D008107)
- **Chemicals:** alcohol (MESH:D000438), fatty acid (MESH:D005227)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12250007/full.md

## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12250007/full.md

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Source: https://tomesphere.com/paper/PMC12250007