Clinical and experimental hepatology · 2025
NADK as a molecular marker to distinguish between alcohol- and non-alcohol-associated liver cirrhosis: A pilot study.
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Park Ki-Hoon, Kim Seok-Hyung, Kim So-Woon, Na Kiyong, Kim Sunyoung, Choi Young-Il, Chung Hyung-Joo, Jung Junyang, Jeong Na Young
Аннотация
AIM OF THE 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.
MATERIAL AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
MATERIAL AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.