Serine palmitoyltransferase long chain subunit 3 is associated with hepatocellular carcinoma in patients with NAFLD

Ijuin,Sho; Oda,Kohei; Mawatari,Seiichi; Taniyama,Ohki; Toyodome,Ai; Sakae,Haruka; Tabu,Kazuaki; Kumagai,Kotaro; Kanmura,Shuji; Tamai,Tsutomu; Moriuchi,Akihiro; Uto,Hirofumi; Ido,Akio

doi:10.3892/mco.2021.2488

Serine palmitoyltransferase long chain subunit 3 is associated with hepatocellular carcinoma in patients with NAFLD

Authors:
- Sho Ijuin
- Kohei Oda
- Seiichi Mawatari
- Ohki Taniyama
- Ai Toyodome
- Haruka Sakae
- Kazuaki Tabu
- Kotaro Kumagai
- Shuji Kanmura
- Tsutomu Tamai
- Akihiro Moriuchi
- Hirofumi Uto
- Akio Ido
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Affiliations: Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan, Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima 890‑8760, Japan, Department of Gastroenterology, National Hospital Organization Kagoshima Medical Center, Kagoshima 892‑0853, Japan, Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki 880‑0003, Japan
Published online on: December 28, 2021 https://doi.org/10.3892/mco.2021.2488
Article Number: 55
Copyright: © Ijuin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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