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Cancer Cell International

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Open Access 01-12-2024 | Hepatocellular Carcinoma | Research

Identification of fatty acids synthesis and metabolism-related gene signature and prediction of prognostic model in hepatocellular carcinoma

Authors: Ai Zhengdong, Xing Xiaoying, Fu Shuhui, Liang Rui, Tang Zehui, Song Guanbin, Yang Li, Tang Xi, Liu Wanqian

Published in: Cancer Cell International | Issue 1/2024

Abstract

Background

Fatty acids synthesis and metabolism (FASM)-driven lipid mobilization is essential for energy production during nutrient shortages. However, the molecular characteristics, physiological function and clinical prognosis value of FASM-associated gene signatures in hepatocellular carcinoma (HCC) remain elusive.

Methods

The Gene Expression Omnibus database (GEO), the Cancer Genome Atlas (TCGA), and International Cancer Genome Consortium (ICGC) database were utilized to acquire transcriptome data and clinical information of HCC patients. The ConsensusClusterPlus was employed for unsupervised clustering. Subsequently, immune cell infiltration, stemness index and therapeutic response among distinct clusters were decoded. The tumor immune dysfunction and exclusion (TIDE) algorithm was utilized to anticipate the response of patients towards immunotherapy, and the genomics of drug sensitivity in cancer (GDSC) tool was employed to predict their response to antineoplastic medications. Least absolute shrinkage and selection operator (LASSO) regression analysis and protein–protein interaction (PPI) network were employed to construct prognostic model and identity hub gene. Single cell RNA sequencing (scRNA-seq) and CellChat were used to analyze cellular interactions. The hub gene of FASM effect on promoting tumor progression was confirmed through a series of functional experiments.

Results

Twenty-six FASM-related genes showed differential expression in HCC. Based on these FASM-related differential genes, two molecular subtypes were established, including Cluster1 and Cluster2 subtype. Compared with cluster2, Cluster1 subtype exhibited a worse prognosis, higher risk, higher immunosuppressive cells infiltrations, higher immune escape, higher cancer stemness and enhanced treatment-resistant. PPI network identified Acetyl-CoA carboxylase1 (ACACA) as central gene of FASM and predicted a poor prognosis. A strong interaction between cancer stem cells (CSCs) with high expression of ACACA and macrophages through CD74 molecule (CD74) and integrin subunit beta 1 (ITGB1) signaling was identified. Finally, increased ACACA expression was observed in HCC cells and patients, whereas depleted ACACA inhibited the stemness straits and drug resistance of HCC cells.

Conclusions

This study provides a resource for understanding FASM heterogeneity in HCC. Evaluating the FASM patterns can help predict the prognosis and provide new insights into treatment response in HCC patients.

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Title: Identification of fatty acids synthesis and metabolism-related gene signature and prediction of prognostic model in hepatocellular carcinoma
Authors: Ai Zhengdong
Xing Xiaoying
Fu Shuhui
Liang Rui
Tang Zehui
Song Guanbin
Yang Li
Tang Xi
Liu Wanqian
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: Cancer Cell International / Issue 1/2024
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-024-03306-4

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Abstract

Background

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