Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

Zhu, Xiao-Ren; Zhu, Jia‐Qi; Chen, Yufei; Liu, Yuan-Yuan; Lu, Jingjing; Sun, Jun; Peng, Shi-Qing; Chen, Min-Bin; Du, Yukou

doi:10.3389/fonc.2022.972744

Cited by 3 publications

(3 citation statements)

References 62 publications

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“…Considering the association of FAS with the immune microenvironment, we further evaluated the ability of FAS to predict immunotherapeutic response to help us distinguish candidates applied for immune therapy in clinical practice. In addition, our results indicated that the patients in the low-FAS group have a higher IPS score, suggesting they have better efficacy for immune checkpoint inhibitors, which is similar to previous studies ( Zhu et al, 2022 ). Additionally, we conducted a K-M survival analysis using a validation cohort and found that the patients receiving immunotherapy with lower FAS had an improved prognosis.…”

Section: Discussionsupporting

confidence: 91%

Integration analysis based on fatty acid metabolism robustly predicts prognosis, dissecting immunity microenvironment and aiding immunotherapy for soft tissue sarcoma

He¹,

Li²,

Feng³

et al. 2023

Front. Genet.

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Background: Soft tissue sarcoma (STS) is a highly malignant tumor with a dismal prognosis. Presently, the dysregulation of fatty acid metabolism has received increasing attention in tumor research, but fewer reports are relevant to STS.Methods: Based on fatty acid metabolism-related genes (FRGs), a novel risk score for STS was developed utilizing univariate analysis and least absolute shrinkage selection operator (LASSO) Cox regression analyses in the STS cohort, which were further validated using the external validation cohort from other databases. Furthermore, independent prognostic analysis, C-index, ROC curves, and nomogram were carried out to investigate the predictive performance of fatty acid-related risk scores. We also analysed the differences in enrichment pathways, the immune microenvironment, gene mutations, and immunotherapy response between the two distinct fatty acid score groups. Moreover, the real-time quantitative polymerase chain reaction (RT-qPCR) was used to further verify the expression of FRGs in STS.Results: A total of 153 FRGs were retrieved in our study. Next, a novel fatty acid metabolism-related risk score (FAS) was constructed based on 18 FRGs. The predictive performance of FAS was also verified in external cohorts. In addition, the independent analysis, C-index, ROC curve, and nomograph also revealed that FAS could serve as an independent prognostic factor for the STS patients. Meanwhile, our results demonstrated that the STS cohort in two distinct FAS groups had different copy number variations, immune cell infiltration, and immunotherapy responses. Finally, the in vitro validation results demonstrated that several FRGs included in the FAS exhibited abnormal expression in STS.Conclusion: Altogether, our work comprehensively and systematically clarifies fatty acid metabolism’s potential roles and clinical significance in STS. The novel individualized score based on fatty acid metabolism may be provided as a potential marker and treatment strategy in STS.

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Section: Discussionsupporting

confidence: 91%

Integration analysis based on fatty acid metabolism robustly predicts prognosis, dissecting immunity microenvironment and aiding immunotherapy for soft tissue sarcoma

He¹,

Li²,

Feng³

et al. 2023

Front. Genet.

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“…Hence, metabolic reprogramming by blocking FA related genes can significantly improve antitumor immunity[ 100 ]. For instance, Zhu et al [ 101 ] used the TCGA database to assess differential expression genes related to FA metabolism. They built a risk prediction model, which could predict not only patient prognosis, but also the therapeutic effect of anti-PD-1 immunotherapy.…”

Section: Impacts Of Lipid Metabolism On Hcc Immunotherapymentioning

confidence: 99%

“…They built a risk prediction model, which could predict not only patient prognosis, but also the therapeutic effect of anti-PD-1 immunotherapy. When patients’ risk score was lower in this model, the efficacy of anti-PD-1 immunotherapy was found to be better[ 101 ]. Cheng et al [ 102 ] described two new HCC cell lines.…”

Section: Impacts Of Lipid Metabolism On Hcc Immunotherapymentioning

confidence: 99%

Lipid metabolism of hepatocellular carcinoma impacts targeted therapy and immunotherapy

Feng¹,

Liu²,

Chen³

et al. 2023

World J Gastrointest Oncol

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Hepatocellular carcinoma (HCC) is a common malignant tumor that affecting many people's lives globally. The common risk factors for HCC include being overweight and obese. The liver is the center of lipid metabolism, synthesizing most cholesterol and fatty acids. Abnormal lipid metabolism is a significant feature of metabolic reprogramming in HCC and affects the prognosis of HCC patients by regulating inflammatory responses and changing the immune microenvironment. Targeted therapy and immunotherapy are being explored as the primary treatment strategies for HCC patients with unresectable tumors. Here, we detail the specific changes of lipid metabolism in HCC and its impact on both these therapies for HCC. HCC treatment strategies aimed at targeting lipid metabolism and how to integrate them with targeted therapy or immunotherapy rationally are also presented.

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HCC: RNA-Sequencing in Cirrhosis

et al. 2023

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Hepatocellular carcinoma (HCC) ranks the most common types of cancer worldwide. As the fourth leading cause of cancer-related deaths, its prognosis remains poor. Most patients developed HCC on the basis of chronic liver disease. Cirrhosis is an important precancerous lesion for HCC. However, the molecular mechanisms in HCC development are still unclear. To explore the changes at the level of transcriptome in this process, we performed RNA-sequencing on cirrhosis, HCC and paracancerous tissues. Continuously changing mRNA was identified using Mfuzz cluster analysis, then their functions were explored by enrichment analyses. Data of cirrhotic HCC patients were obtained from TCGA, and a fatty acid metabolism (FAM)-related prognostic signature was then established. The performance and immunity relevance of the signature were verified in internal and external datasets. Finally, we validated the expression and function of ADH1C by experiments. As a result, 2012 differently expressed mRNA were identified by RNA-sequencing and bioinformatics analyses. Fatty acid metabolism was identified as a critical pathway by enrichment analyses of the DEGs. A FAM-related prognostic model and nomogram based on it were efficient in predicting the prognosis of cirrhotic HCC patients, as patients with higher risk scores had shorter survival time. Risk scores calculated by the signature were then proved to be associated with a tumor immune environment. ADH1C were downregulated in HCC, while silence of ADH1C could significantly promote proliferation and motility of the HCC cell line.

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Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

Cited by 3 publications

References 62 publications

Integration analysis based on fatty acid metabolism robustly predicts prognosis, dissecting immunity microenvironment and aiding immunotherapy for soft tissue sarcoma

Integration analysis based on fatty acid metabolism robustly predicts prognosis, dissecting immunity microenvironment and aiding immunotherapy for soft tissue sarcoma

Lipid metabolism of hepatocellular carcinoma impacts targeted therapy and immunotherapy

HCC: RNA-Sequencing in Cirrhosis

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