Interactions between the metabolic reprogramming of liver cancer and tumor microenvironment

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 14, 2025

Metabolic reprogramming is one of the major biological features malignant tumors, playing a crucial role in initiation and progression cancer. The tumor microenvironment consists various non-cancer cells, such as hepatic stellate cancer-associated fibroblasts (CAFs), immune well extracellular matrix soluble substances. In liver cancer, metabolic not only affects its own growth survival but also interacts with other cells by influencing expression release metabolites cytokines (such lactate, PGE2, arginine). This interaction leads to acidification restricts uptake nutrients resulting competition symbiosis. At same time, neighboring during proliferation differentiation processes impacts immunity. article provides comprehensive overview crosstalk between cancer their microenvironment, deepening our understanding relevant findings pathways. contributes further regulation development evasion mechanisms while providing assistance advancing personalized therapies targeting pathways for anti-cancer treatment.

Language: Английский

---

Multi-omics integration analysis of the amino-acid metabolism-related genes identifies putatively causal variants of ACCS associated with hepatitis B virus-related hepatocellular carcinoma survival

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 18, 2025

Amino acid metabolism (AAM) reprogramming plays a crucial role in hepatocellular carcinoma (HCC), but its genetic pathophysiology was not fully elucidated. Therefore, we employed summary data-based Mendelian randomization (SMR) approach to identify putative causal effects of the AAM-related genes on hepatitis B virus (HBV)-HCC survival via integrating multi-omics data. Multivariate Cox proportional hazards regression models were used evaluate associations between variants and overall (OS) HBV-HCC patients (n = 866). Next, developed pathway-specific risk score (GRS) comprising AAM pathway. Subsequently, SNPs prioritized using SMR by OS data with expression quantitative trait loci (eQTLs) DNA methylation QTLs (mQTLs) from blood, as well eQTLs liver tissues. We identified 23 independent associated OS, GRS derived significant predictor OS. The addition significantly improved predictive performance 5-year model (AUC increased 72.04% 84.67%, P < 0.001). By mQTLs variant rs2074038 across ACCS expression, methylation. Furthermore, integration eQTL revealed that levels worse Mechanistically, bioinformatics annotation luciferase reporter assays further demonstrated contributes progression allele-specific regulation expression. This study novel functional SNP poor survival, likely mediated These findings suggest is potential therapeutic target highlight need for validation clinical settings.

Language: Английский

---

Biosocial Determinants of Health Among Patients with Chronic Liver Disease and Liver Cancer

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 844 - 844

Published: Feb. 28, 2025

Metabolic disorders and chronic liver disease (CLD) play crucial roles in the development progression of cancer (LC). Since ethnic minority population increasingly suffers from CLD LC, it is vital to understand biosocial factors contributing LC. The 'All Us' database, with significant participation populations, provides a valuable tool for studies different racial/ethnic groups. Using databases, including 'The Cancer Genome Atlas', this study aimed data, confounding like lack immunization, comorbidities, socioeconomic status (SES) barriers were analyzed cohort 33767 [non-alcoholic fatty disease, alcoholic Hepatitis B C] patients. Among 556 LC patients 92% had CLD. hypoxanthine known be increased urine patients, purine metabolic pathway genes using databases validated publicly available RNASeq data. We identified several associated Hispanic (HA) African American (AA) populations compared non-Hispanic White (NHW) populations. HA AA suffer high SES barriers. While most related upregulated xanthine dehydrogenase (XDH), which converts uric acid, showed downregulation tumor normal tissues. TCGA data among groups that only Asian (AN) tumors XDH expression was significantly lower NHW. decreased mRNA AN benign tissues further RNAseq datasets. Survival analysis confirmed poor overall survival their tumors. Our population. This also as critical alteration has clinical significance

Language: Английский

---

Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 9, 2025

Hepatocellular carcinoma (HCC) is the main phenotype of liver cancer with a poor prognosis. Copper vital in function, and HCC cells rely on it for growth metastasis, leading to cuproplasia. Excessive copper can induce cell death, termed cuproptosis. Tumor microenvironment (TME) pivotal HCC, especially immunotherapy, closely related TME pathogenesis. However, how these two mechanisms contribute intriguing. We conducted latest progress literature cuproplasia cuproptosis summarized their specific roles treatment strategies. The relationship role have been deeply summarized. Cuproplasia fosters formation, angiogenesis, whereas may alleviate mitochondrial dysfunction hypoxic conditions TME. Inhibiting enhancing are essential achieving therapeutic efficacy HCC. An in-depth analysis within unveils opposing nature impact regulation. Grasping equilibrium between factors crucial deeper understanding shed light novel directions treating

Language: Английский

---

Glutamate promotes CCL2 expression to recruit tumor-associated macrophages by restraining EZH2-mediated histone methylation in hepatocellular carcinoma

OncoImmunology, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 24, 2025

Glutamate is well-known as metabolite for maintaining the energy and redox homeostasis in cancer, moreover it also primary excitatory neurotransmitter central nervous system. However, whether glutamatergic signaling can regulate hepatocellular carcinoma (HCC) progression specific regulatory mechanisms are unknown. In present study, we found that glutamate its receptor NMDAR2B were significantly elevated HCC patients, which predicts poor prognosis. could upregulate CCL2 expression on hepatoma cells further enhance capability of tumor to recruit tumor-associated macrophages (TAMs). Mechanistically, facilitate through NMDAR pathway by decreasing EZH2, regulates H3K27me3 levels promoter, rather than affecting DNA methylation. Moreover, inhibiting with MK801 delay growth, reduced TAMs implanted Hepa1-6 mouse models. Our work suggested induce promote TAM infiltration negatively regulating EZH2 cells, might serve a potential prognostic marker therapeutic target patients.

Language: Английский

---

Interactions between Helicobacter pylori infection and host metabolic homeostasis: A comprehensive review

Helicobacter, Journal Year: 2023, Volume and Issue: 28(6)

Published: Oct. 23, 2023

Abstract The microbiota actively and extensively participates in the regulation of human metabolism, playing a crucial role development metabolic diseases. Helicobacter pylori ( H. ), when colonizing gastric epithelial cells, not only induces local tissue inflammation or malignant transformation but also leads to systemic partial changes host metabolism. These shifts can be mediated through direct contact, toxic components, indirect immune responses. Consequently, they influence various molecular events that impact nutritional status iron absorption host. Unraveling intricate diverse interaction links between metabolism modulation is essential for understanding pathogenesis mechanisms developing targeted treatments related However, significant challenges persist comprehensively complex association networks among itself, infected host's status, microbiome, response. Previous metabolomics research has indicated infection eradication may selectively shape metabolite microbial profiles lesions. Yet, it remains largely unknown how these pathways, including isovaleric acid, cholesterol, fatty acids, phospholipids, specifically modulate carcinogenesis affect serum consequently leading metabolic‐associated contribution metabolisms still lacks conclusive evidence. In this review, we summarize recent advances clinical evidence highlighting associations chronic diseases, as well its potential regulatory patterns.

Language: Английский

---

Unraveling the Sweet Secrets of HCC: Glucometabolic Rewiring in Hepatocellular Carcinoma

Technology in Cancer Research & Treatment, Journal Year: 2023, Volume and Issue: 22

Published: Jan. 1, 2023

Hepatocellular carcinoma (HCC) is the primary form of liver cancer. It causes ∼ 800 000 deaths per year, which expected to increase due increasing rates obesity and metabolic dysfunction associated steatotic disease (MASLD). Current therapies include immune checkpoint inhibitors, tyrosine kinase monoclonal antibodies, but these are not satisfactorily effective often come with multiple side effects recurrences. Metabolic reprogramming plays a significant role in HCC progression conserved between tumor types. Thus, targeting rewired pathways could provide an attractive option for cells alone or conjunction existing treatments. Therefore, there urgent need identify novel targets involved cancer-mediated HCC. In this review, we overview molecular rewiring glucose metabolism understand better concepts that might widen therapeutic window against deadly

Language: Английский

---

Hepatitis C virus infection and Parkinson’s disease: insights from a joint sex-stratified BioOptimatics meta-analysis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 1, 2024

Language: Английский

---

Analysis of nitrogen metabolism-related gene expression in hepatocellular carcinoma to establish relevant indicators for prediction of prognosis and guidance of immunotherapy

Computer Methods in Biomechanics & Biomedical Engineering, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 17

Published: Dec. 14, 2024

The prognosis of cancers is strongly connected with nitrogen metabolism (NM), which plays a critical role in the microenvironment and growth tumors. It unsubstantiated, however, how important NM-related genes are for hepatocellular carcinoma (HCC).

Language: Английский

---

Atomic elementary flux modes explain the steady state flow of metabolites in large-scale flux networks

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Abstract Steady state fluxes are a measure of cellular activity under metabolic homoeostasis, but understanding how individual substrates metabolized remains challenge in large-scale networks. Pathway-based approaches such as elementary flux mode (EFM) analysis limited to small networks due the combinatorial explosion pathways and ambiguity decomposing onto EFMs. Here, we present an alternative approach explain terms steady flow their atomic constituents. We refer these modes (AEFMs) show that computations involving AEFMs orders magnitude faster than standard Using our approach, enumerate carbon nitrogen five genome-scale models compute AEFM decomposition estimated HepG2 liver cancer cell line. Our results systematically characterize remodelling and, on network, predict glutamine metabolism through recently discovered non-canonical TCA cycle.

Language: Английский

---