Published online May 19, 2026. doi: 10.5498/wjp.v16.i5.117187
Revised: January 9, 2026
Accepted: February 12, 2026
Published online: May 19, 2026
Processing time: 141 Days and 0.6 Hours
Hepatocellular carcinoma (HCC), a prevalent primary liver cancer with high mortality, is often linked to chronic liver disease. Despite advances in treatment, prognosis remains poor due to high recurrence and metastasis. Alcohol dehydrogenase 4 (ADH4), involved in ethanol metabolism, is understudied in HCC regarding its expression, clinical relevance, and prognosis. Additionally, psychological distress in HCC patients may affect both quality of life and disease progr
To investigate the expression level of ADH4 in HCC and its relationship with tumor invasiveness, patient survival prognosis, and anxiety-depression status to provide evidence for the clinical diagnosis, treatment, and comprehensive mana
A retrospective cohort study design was adopted, including 148 patients with HCC who underwent surgical resection between January 2018 and January 2023 with complete clinicopathological data and follow-up inf
The mean maximum tumor diameter in the ADH4 low expression group (6.2 ± 2.5 cm) was significantly larger than that in the high expression group (4.5 ± 1.8 cm) (t = -4.218, P < 0.001). ADH4 expression was positively correlated with the degree of tumor differentiation (r = 0.432, P < 0.001), and the proportion of high ADH4 expression in well-differentiated tumors (76.9%) was significantly higher than that in poorly differentiated tumors (27.3%). The MVI positivity rate in the low expression group (73.0%) was significantly higher than that in the high expression group (32.4%) (χ² = 22.563, P < 0.001). Survival analysis showed that the 1-year and 3-year survival rates in the high expression group (82.4%, 55.4%) were significantly higher than those in the low expression group (60.8%, 29.7%) (χ² = 15.347, P < 0.001). Multivariate Cox regression analysis confirmed that low ADH4 expression [hazard ratio (HR) = 0.486, 95%CI: 0.305-0.775, P = 0.002], large tumor size (HR = 1.768, 95%CI: 1.135-2.750, P = 0.012), and MVI positivity (HR = 2.047, 95%CI: 1.315-3.186, P = 0.002) were independent risk factors for poor prognosis in patients with HCC. Psychological assessment revealed that HAMA and HAMD scores in the low expression group (13.8 ± 4.2 points, 15.6 ± 4.5 points) were significantly higher than those in the high expression group (10.2 ± 3.5 points, 11.5 ± 3.8 points) (t = -5.217, t = -5.528, respectively, both P < 0.001), and ADH4 expression was negatively correlated with both HAMA and HAMD scores (r = -0.456, r = -0.482, respectively, both P < 0.001).
Low ADH4 expression in HCC tissues is closely associated with enhanced tumor invasiveness, larger tumor volume, lower degree of differentiation, and higher MVI incidence. Patients with high ADH4 expression have better anxiety and depression states but poor survival prognosis. ADH4 may be a potential biomarker for assessing the severity, prognosis, and psychological status of patients with HCC, providing an important reference for per
Core Tip: Low alcohol dehydrogenase 4 (ADH4) expression in hepatocellular carcinoma correlates with larger tumors, poor differentiation, high microvascular invasion, reduced 1-year and 3-year survival, and elevated anxiety-depression scores. Multivariate analysis identifies low ADH4 as an independent poor prognostic factor. These findings suggest ADH4 is a valuable biomarker for assessing tumor aggressiveness, predicting outcomes, and identifying patients requiring intensive therapy and psychosocial support, thus enabling personalized oncological and mental-health interventions to improve overall prognosis and quality of life.