NADK as a molecular marker to distinguish between alcohol- and non-alcohol-associated liver cirrhosis: A pilot study

We investigated whether nicotinamide adenine dinucleotide kinase (NADK) expression is selectively diminished in alcohol-associated liver cirrhosis (AC), and evaluated its potential as a biomarker for this condition.

Human liver samples were obtained during liver transplantation or resection procedures at Kosin University Gospel Hospital and classified into two groups: AC and non-AC (NAC). NAD⁺ and NADP⁺ levels were measured using liquid chromatography-mass spectrometry (LC-MS). RNA-seq data from the NCBI Gene Expression Omnibus were utilized to identify AC-specific differentially expressed genes (DEGs). Multi-level expression analyses and immunohistochemistry were performed to assess NADK expression in liver tissues.

LC-MS analysis indicated a significant reduction in NAD⁺ and NADP⁺ levels in AC patients compared to both normal and NAC groups, with a corresponding increase in the NAD⁺/NADP⁺ ratio (AC = 3.93, NAC = 2.75, normal = 2.64). We identified 881 AC-specific DEGs, including 27 kinase-encoding genes. Multi-level expression analyses confirmed a significant decrease in NADK gene expression in AC patients. Immunohistochemistry showed a marked reduction in NADK protein expression in AC patients, underscoring its involvement in altered metabolic processes.

This study revealed a distinct decrease in NADK expression in AC, suggesting its utility as a molecular marker for diagnosing and understanding metabolic dysregulation in these patients. These findings provide a foundation for developing targeted therapeutic strategies for alcohol-associated liver cirrhosis.