Open Access

ARTICLE

Identification prognostic features related to sphingolipid metabolism and experimental validation of TRIM47 in hepatocellular carcinoma

JIAN TANG¹, CHENQIANG ZHU¹, YUN CHEN¹, YUNLONG WU¹, MING HE¹, YI ZHOU², MINGHUA XIE^2,*

1 Department of Intensive Care Unit, The First People’s Hospital of Linping District, Hangzhou, China
2 Department of Pharmacy, The First People’s Hospital of Linping District, Hangzhou, China

* Corresponding Author: MINGHUA XIE. Email:

(This article belongs to the Special Issue: Navigating the Interplay of Cancer, Autophagy, ER Stress, Cell Cycle and Apoptosis: Mechanisms, Therapies, and Future Directions)

BIOCELL 2024, 48(4), 639-651. https://doi.org/10.32604/biocell.2024.047562

Received 09 November 2023; Accepted 14 December 2023; Issue published 09 April 2024

Abstract

Background: The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma (HCC) remains unclear. This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis, immune response, and drug sensitivity. Methods: Data were obtained from The Cancer Genome Atlas (TCGA)-Hepatocellular Carcinoma (LIHC) and Gene Expression Omnibus (GEO, GSE14520 datasets). 47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. After classifying HCC samples using the Non-negative Matrix Factorization (NMF) clustering method, differentially expressed genes were screened. Then, 8 risk genes were obtained by univariate analysis, survival random forest reduction and lasso analysis. The expression of 8 risk genes was verified in vitro. Results: 8 risk genes were used to construct the Sphingolipid score model. High-Sphingolipid score predicted poor prognosis of HCC patients. Sphingolipid score was associated with immune checkpoints (IL-1B, TLR4, TGFB1, and IL-10), immune cells (Th2, Treg, MDSC, Neutrophil, Fibroblasts and macrophage), and MAPK Cascade. In the High-Sphingolipid score group, a significantly higher proportion of patients with TP53 (p53) mutations was significantly higher (56%). Furthermore, patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy drugs. In vitro validation showed that compared with normal liver cells LX-2, TRIM47, and S100A9 significantly increased in liver cancer cells Hep G2, MHCC-97H, and Hep3B2.1-7, while SLC1A7, LPCAT1, and CFHR4 significantly decreased. Silencing TRIM47 reduced the proliferation and promoted apoptosis. The levels of ceramide synthesis-related indexes (CERS1, CERS6, CERS5, and SPTLC2) increased, and the ACER3 related to catalytic hydrolysis decreased. Conclusion: We constructed a sphingolipid metabolism-related prognostic signature (Sphingolipid score) based on 8 risk genes. TRIM47 may affect the development of liver cancer by regulating the relevant indicators of ceramide synthesis and catalytic hydrolysis.

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Supplementary Material

Supplementary Material File

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