The altered lipidome of hepatocellular carcinoma

Tan, Shawn Lu Wen; Israeli, Erez; Ericksen, Russell; Chow, Pierce Kah‐Hoe; Han, Weiping

doi:10.1016/j.semcancer.2022.02.004

Cited by 20 publications

(16 citation statements)

References 181 publications

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“…BAs are closely associated with HCC [ 43 ]. They engage in the carcinogenesis of HCC by directly binding to the receptors and activating signaling pathways that induce changes in the local immune microenvironment and metabolic status of liver cells and cause DNA damage [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Development of a Bile Acid-Related Gene Signature for Predicting Survival in Patients with Hepatocellular Carcinoma

Gang

Guan

Yang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Hepatocellular carcinoma (HCC) is one of the most common diseases that threaten millions of lives annually. Evidence supports that bile acid (BA) affects HCC through inflammation, DNA damage, or other mechanisms. Methods. A total of 127 BA-associated genes were analyzed in HCC tumor and nontumor samples using The Cancer Genome Atlas data. Genes correlated to the prognosis of patients with HCC were identified using univariate and multivariate Cox regression analyses. Furthermore, a prediction model with identified genes was constructed to evaluate the risk of patients with HCC for prognosis. Results. Out of 26 genes with differential expressions between the HCC and nontumor samples, 19 and 7 genes showed upregulated and downregulated expressions, respectively. Three genes, NPC1, ABCC1, and SLC51B, were extrapolated to construct a prediction model for the prognosis of patients with HCC. Conclusion. The three-gene prediction model was more reliable than the pathological staging characters of the tumor for the prognosis and survival of patients with HCC. In addition, the upregulated genes facilitating the transport of BAs are associated with poor prognosis of patients with HCC, and genes of de novo synthesis of BAs benefit patients with HCC.

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Section: Discussionmentioning

confidence: 99%

Development of a Bile Acid-Related Gene Signature for Predicting Survival in Patients with Hepatocellular Carcinoma

Gang

Guan

Yang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Enrichment analysis revealed that the significantly altered metabolites are involved in important metabolic pathways, including the Warburg effect, gluconeogenesis, citric acid cycle, several amino acid‐related pathways, glycolysis, lipid biosynthesis and β‐oxidation (Figure 1C). Of note, alterations in these metabolic pathways have been described in advanced NASH and NASH‐associated HCC, 14 suggesting that miR‐21 may be contributing for carcinogenesis during NAFLD progression through changes in the lipidome. In parallel, we also analysed the serum metabolomic profile of these patients and observed that patients with ‘high’ hsa‐miR‐21‐5p expression in the liver displayed decreased levels of several glycerophospholipids, in particular some species of LPCs (Figure S3 and Table S4), that negatively mirror the profile observed in the liver, suggesting they are less abundantly detected in serum as a result of its liver accumulation.…”

Section: Resultsmentioning

confidence: 99%

miR‐21‐5p promotes NASH‐related hepatocarcinogenesis

Rodrigues

Afonso

Simão

et al. 2023

Liver International

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Background and AimsThe mechanisms governing the progression of non‐alcoholic fatty liver disease (NAFLD) towards steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain elusive. Here, we evaluated the role of hsa‐miRNA‐21‐5p in NASH‐related hepatocarcinogenesis.MethodsHepatic hsa‐miR‐21‐5p expression was evaluated in two cohorts of patients with biopsy‐proven NAFLD (n = 199) or HCC (n = 366 HCC and n = 11 NAFLD‐HCC). Serum/liver metabolomic profiles were correlated with hsa‐miR‐21‐5p in NAFLD obese patients. Wild‐type (WT) and Mir21 KO mice were fed a choline‐deficient, amino acid‐defined (CDAA) diet for 32 and 66 weeks to induce NASH and NASH‐HCC, respectively.ResultsIn obese individuals, hsa‐miR‐21‐5p expression increased with NAFLD severity and associated with a hepatic lipotoxic profile. CDAA‐fed WT mice displayed increased hepatic mmu‐miR‐21‐5p levels and progressively developed NASH and fibrosis, with livers presenting macroscopically discernible pre‐neoplastic nodules, hyperplastic foci and deregulated cancer‐related pathways. Mir21 KO mice exhibited peroxisome‐proliferator‐activated receptor α (PPARα) activation, augmented mitochondrial activity, reduced liver injury and NAS below the threshold for NASH diagnosis, with the pro‐inflammatory/fibrogenic milieu reversing to baseline levels. In parallel, Mir21 KO mice displayed reduced number of pre‐neoplastic nodules, hepatocyte proliferation and activation of oncogenic signalling, being protected from NASH‐associated carcinogenesis. The hsa‐miRNA‐21‐5p/PPARα pathway was similarly deregulated in patients with HCC‐ or NASH‐related HCC, correlating with HCC markers and worse prognosis.ConclusionsHsa‐miR‐21‐5p is a key inducer of whole‐spectrum NAFLD progression, from simple steatosis to NASH and NASH‐associated carcinogenesis. The inhibition of hsa‐miR‐21‐5p, leading to a pro‐metabolic profile, might constitute an appealing therapeutic approach to ameliorate NASH and prevent progression towards HCC.

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“…They are the main component of biological membranes. Studies of the lipidomic profile in human samples of both NAFLD and HBV-associated HCCs reported a significant reduction of PGLs composed by PUFAs (such as arachidonic acid -C20:4-), often coupled by an increase in MUFAs containing ones (such as oleic acid -C18:1-) [ 93 ]. On the one hand, this lipid imbalance could be due to the high degree of PUFAs peroxidation associated with the typical HCC high oxidative damage burden.…”

Section: A Comprehensive Picture Of Liver Cancer Cell Metabolismmentioning

confidence: 99%

“…Ceramides are considered anti-cancer factors promoting apoptosis and cell cycle arrest [ 117 , 118 ] and are typically reduced in human HCC [ 119 , 120 , 121 , 122 , 123 , 124 , 125 ]. Furthermore, ceramides may be converted into more complex sphingolipids, such as sphingomyelin (SM), sphingosine 1-phosphate (S1P) and glucosylceramides (GlcCer) [ 93 ] which are considered pro-tumoral factors and whose production is enhanced during HCC pathogenesis [ 126 , 127 , 128 , 129 , 130 , 131 , 132 ]. Interestingly, a lipidomic analysis showed that SM levels are lower in HCCs from viral origin compared to HCCs from NAFLD origin [ 98 ].…”

Section: A Comprehensive Picture Of Liver Cancer Cell Metabolismmentioning

confidence: 99%

Metabolic Reprogramming of HCC: A New Microenvironment for Immune Responses

Foglia

Beltrà

Sutti

et al. 2023

IJMS

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Hepatocellular carcinoma is the most common primary liver cancer, ranking third among the leading causes of cancer-related mortality worldwide and whose incidence varies according to geographical area and ethnicity. Metabolic rewiring was recently introduced as an emerging hallmark able to affect tumor progression by modulating cancer cell behavior and immune responses. This review focuses on the recent studies examining HCC’s metabolic traits, with particular reference to the alterations of glucose, fatty acid and amino acid metabolism, the three major metabolic changes that have gained attention in the field of HCC. After delivering a panoramic picture of the peculiar immune landscape of HCC, this review will also discuss how the metabolic reprogramming of liver cancer cells can affect, directly or indirectly, the microenvironment and the function of the different immune cell populations, eventually favoring the tumor escape from immunosurveillance.

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The altered lipidome of hepatocellular carcinoma

Cited by 20 publications

References 181 publications

Development of a Bile Acid-Related Gene Signature for Predicting Survival in Patients with Hepatocellular Carcinoma

Development of a Bile Acid-Related Gene Signature for Predicting Survival in Patients with Hepatocellular Carcinoma

miR‐21‐5p promotes NASH‐related hepatocarcinogenesis

Metabolic Reprogramming of HCC: A New Microenvironment for Immune Responses

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