The prevalence of
non-alcoholic fatty liver disease (
NAFLD) is continuously increasing, with the proportion of patients with liver
carcinogenesis due to non-
alcoholic steatohepatitis (NASH) rising accordingly. Although it is important to identify individuals with hepatic
carcinogenesis among patients with
NAFLD, useful
biomarkers have not yet been established. Previously, in a mouse model of
diabetes mellitus without genetic modifications, we reported that a high-fat diet increases
serine palmitoyltransferase long chain subunit 3 (SPTLC3) expression in liver tissue, accompanied by high frequency of liver
carcinogenesis.
Serine palmitoyltransferase (SPT) catalyzes the metabolism of
fatty acids, particularly
sphingolipid synthesis, and SPTLC3 has been identified as its catalytic subunit, but its role in
liver disease is unclear. In the present study, the importance of SPTLC3 in
NAFLD development was investigated. SPTLC3
mRNA expression was observed in a
liver cancer cell line and in liver tissues from patients with
NAFLD and
liver cancer. In total, 99 patients with
NAFLD (66 without
hepatocellular carcinoma (HCC) and 33 with HCC were recruited, having been diagnosed by liver biopsy or imaging, along with 6 healthy volunteers (HVs). Serum was collected from patients and HVs, and SPTLC3 level was assessed by ELISA. SPTLC3 expression was higher in non-cancerous compared with that in cancerous liver tissues. Serum SPTLC3 levels were negatively correlated with platelet count and positively correlated with
hyaluronic acid levels, suggesting an association with
liver fibrosis. Moreover, SPTLC3 levels were significantly higher in the HCC group than in the HV and
NAFLD groups. Multivariate analysis of HCC-related factors identified platelets,
alanine transferase,
albumin and SPTLC3 as independent factors associated with HCC. Furthermore, in patients with other chronic
liver diseases (
hepatitis B and C, and
alcoholic liver disease), no significant differences in serum SPTLC3 levels were observed between patients with or without HCC. Thus, SPTLC3 expression increases specifically with the progression of
NAFLD. Overall, the present results indicate that SPTLC3 may be involved in the development of liver
carcinogenesis during
NAFLD.