Fatty Acid Synthase Is the Key Regulator of Fatty Acid Metabolism and Is Related to Immunotherapy in Bladder Cancer

Xiong, Qiao; Feng, Dechao; Wang, Ziwei; Ying, Yidie; Che, Xu; Wang, Qiang; Zeng, Shuxiong; Yang, Lu

doi:10.3389/fimmu.2022.836939

Cited by 27 publications

(14 citation statements)

References 55 publications

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“…Besides, lipid pathways which included arachidonic acid, α-linolenic acid, linoleic acid, and fatty acid metabolism were all more dynamic in the low TMMSscore group. One study highlighted that fatty acid metabolism was an important intermediate in lipid metabolism, was involved in the origin and evolution of several metabolic diseases and cancers, while this study also highlighted that fatty acid synthase took on a critical signi cance in BC fatty acid metabolism and could be a potential target for immunotherapy 39 . Another study reported that tyrosine kinases in tyrosine metabolism regulated the cell growth process through different signaling pathways such as growth, migration, differentiation and metabolism and had the potential to become a personalized anti-cancer therapeutic regimen 40 .…”

Section: Discussionmentioning

confidence: 93%

A novel molecular classification based on TP53 mutation to predict bladder cancer prognosis and immunotherapy efficacy

Wang,

Li,

Lei

et al. 2024

Preprint

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Background The efficacy of TP53, the most widely researched mutation genetic genes in tumor, in tumor metabolic reprogramming remains unclear. Methods The differential analysis of gene expression data information of TP53 mutation and TP53 wild-type patients were conducted to identify TP53 mutation-associated metabolic genes (TMGs), which were used to identify and verify a TP53 mutation-associated metabolic signature (TMMS). Comprehensive bioinformatics analyses were performed to explore biological interpretability and clinical application value of TMMS. Results According to TP53 mutation, 218 TMGs were detected. The TMMSscore including GFPT2, ATP6V1C2, IMPDH1, CKMT2, PPT2, CAD, HNMT, INPP1 and PLCH1 genes were constructed and verified to determine a low TMMSscore group, which showed more favorable prognosis in the TCGA and GEO cohort compared to a high TMMSscore group. The high TMMSscore group contained more reprogrammed metabolic pathways, which had glycan-related metabolism and less immune infiltration. The low TMMSscore group showed more immune cell infiltration, which included anti-tumor cells in BC, for instance CD8(+) T cells, Treg cells and less metabolic reprogramming. In two immunotherapy cohorts of anti-PD-1 treated lung and kidney cancers, TMMSscore was used to distinguish a low TMMSscore group with better immunotherapy efficacy from a high TMMSscore group and identify a key differentially expressed genes (DEGs) termed COL1A2. In immunohistochemistry experiments on three tumor tissue samples and three normal tissue samples from three bladder cancer patients, COL1A2 showed high expression characteristics in tumors. Conclusions The TMMS based on metabolic genes affected by TP53 mutations predicted the prognosis of BC and develop a guiding strategy for immune checkpoint therapy. This research brought a new insight into the involvement of TP53 mutations in tumor metabolic reprogramming.

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Section: Discussionmentioning

confidence: 93%

A novel molecular classification based on TP53 mutation to predict bladder cancer prognosis and immunotherapy efficacy

Wang,

Li,

Lei

et al. 2024

Preprint

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“…In bladder cancer, FASN is a key regulator of fatty acid metabolism and is associated with immunotherapy. In addition, immune analysis showed that FASN was significantly associated with several immune cells ( 52 ). Another enzyme, HSD17B4, is also involved in the synthesis and elongation of unsaturated fatty acids ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring functional metabolites and proteomics biomarkers in late-preterm and natural-born pigs

Chong,

Wang,

Zhong

et al. 2024

Front. Vet. Sci.

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IntroductionPigs are often used to study the intestinal development of newborns, particularly as preterm pig models that mimic the intestinal growth of human preterm infants. Neonatology’s study of delivery mode’s impact on neonatal development is crucial.MethodsWe established 14 newborn pigs delivered via cesarean sections (C-section, at 113 days of gestational age, CS group) and 8 naturally born pigs were used as controls (at 114 days of gestational age, NF group). The impact of two alternative delivery procedures (C-section and natural birth) on the levels of short-chain fatty acids (SCFAs) and organic acids in the hepatic and intestines of newborn pigs were compared using metabolomics. The underlying molecular pathways are examined at the “protein-metabolite” level by integrating proteomic data.ResultsThe findings demonstrated that the mode of delivery changed the metabolism of SCFAs in newborn pigs, perhaps by affecting the physiology levels of cyclic intermediates such as lactate and malate in the pyruvate metabolic pathway. Additionally, by participating in the fatty acid metabolism pathway, two distinct proteins (FASN and HSD17B4) may impact the physiological concentration of these tiny metabolites.DiscussionIn conclusion, this study provided reliable animal model data for understanding the physiological SCFA metabolic information and its affecting mechanism of large-gestational age preterm infants.

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“…The liver, as the core site of lipid metabolism, plays a vital role in the lipid cycle [ 25 ]. FAS, CACT, and ACC all contribute to the control of lipid synthesis [ 39 , 40 , 41 ]. In our study, FAS, CACT, and ACC activity were down-regulated by Aurantiochytrium sp.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dietary Supplementation with Aurantiochytrium sp. on Zebrafish Growth as Determined by Transcriptomics

Yang

Huang

et al. 2022

Animals

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The marine protist Aurantiochytrium produces several bioactive chemicals, including EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), and other critical fish fatty acids. It has the potential to improve growth and fatty acid profiles in aquatic taxa. This study evaluated zebrafish growth performance in response to diets containing 1% to 3% Aurantiochytrium sp. crude extract (TE) and single extract for 56 days. Growth performance was best in the 1% TE group, and therefore, this concentration was used for further analyses of the influence of Aurantiochytrium sp. Levels of hepatic lipase, glucose-6-phosphate dehydrogenase, acetyl-CoA oxidase, glutathione peroxidase, and superoxide dismutase increased significantly in response to 1% TE, while malic enzyme activity, carnitine lipid acylase, acetyl-CoA carboxylase, fatty acid synthase, and malondialdehyde levels decreased. These findings suggest that Aurantiochytrium sp. extract can modulate lipase activity, improve lipid synthesis, and decrease oxidative damage caused by lipid peroxidation. Transcriptome analysis revealed 310 genes that were differentially expressed between the 1% TE group and the control group, including 185 up-regulated genes and 125 down-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analyses of the differentially expressed genes revealed that Aurantiochytrium sp. extracts may influence liver metabolism, cell proliferation, motility, and signal transduction in zebrafish.

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Fatty Acid Synthase Is the Key Regulator of Fatty Acid Metabolism and Is Related to Immunotherapy in Bladder Cancer

Cited by 27 publications

References 55 publications

A novel molecular classification based on TP53 mutation to predict bladder cancer prognosis and immunotherapy efficacy

A novel molecular classification based on TP53 mutation to predict bladder cancer prognosis and immunotherapy efficacy

Exploring functional metabolites and proteomics biomarkers in late-preterm and natural-born pigs

Effects of Dietary Supplementation with Aurantiochytrium sp. on Zebrafish Growth as Determined by Transcriptomics

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