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

作     者：JIAN TANG CHENQIANG ZHU YUN CHEN YUNLONG WU MING HE YI ZHOU MINGHUA XIE 

作者机构：Department of Intensive Care UnitThe First People’s Hospital of Linping DistrictHangzhouChina Department of PharmacyThe First People’s Hospital of Linping DistrictHangzhouChina 

出 版 物：《BIOCELL》 (生物细胞（英文）)

年 卷 期：2024年第48卷第4期

页      面：639-651页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：The work was supported by funds from The Science and Technology Project of Hangzhou City(Agriculture and Social Development,No.2016007)&(Agriculture and Social Development,No.20201231Y131)&(Social Development,No.20140633B57) The Science and Technology Project of Yuhang District,Hangzhou City(Nos.2017002&2014003) The Health Science and Technology Project of Hangzhou City(No.2015B32) Zhejiang Provincial Natural Science Foundation of China under Grant(No.LTGY23H160006) The Health Science and Technology Project of Zhejiang Province(No.2023XY009) 

主　　题：Hepatocellular carcinoma Sphingolipid metabolism TRIM47 Prognosis 

摘      要：Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains *** study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug ***: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)*** classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were ***,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso *** expression of 8 risk genes was verified in ***:8 risk genes were used to construct the Sphingolipid score ***-Sphingolipid score predicted poor prognosis of HCC *** score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDSC,Neutrophil,Fibroblasts and macrophage),and MAPK *** 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 *** 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 *** TRIM47 reduced the proliferation and promoted *** levels of ceramide synthesis-related indexes(CERS1,CERS6,CERS5,and SPTLC2)increased,and the ACER3 related to catalytic hydrolysis ***:We constructed a sphingolipid metabolism-related prognostic signature(Sphingolipid score)based on 8 risk ***47 may affect the development of liver cancer by regulating the relevant indicators of