Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Language: Английский

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Hepatocellular Carcinoma: Latest Research in Pathogenesis, Detection and Treatment

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12224 - 12224

Published: July 31, 2023

The most common form of primary liver malignancy is hepatocellular carcinoma (HCC) [...]

Language: Английский

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IGF2BP1/AIFM2 axis regulates ferroptosis and glycolysis to drive hepatocellular carcinoma progression

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111660 - 111660

Published: Feb. 1, 2025

Language: Английский

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Survival Benefits of Transarterial Chemoembolization Plus Ablation Therapy in Patients With Intermediate or Advanced Hepatocellular Carcinoma: A Propensity Score Matching Study

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 483 - 497

Published: March 1, 2025

To evaluate the survival outcomes of patients with intermediate to advanced hepatocellular carcinoma (HCC), who underwent transarterial chemoembolization (TACE) alone were compared those a combination TACE and ablation therapy. This study retrospectively evaluated 536 HCC in our hospital from July 2016 November 2022. All TACE, subset also receiving ensure comparability, propensity score matching (PSM) was performed. We then overall (OS) progression-free (PFS) between these two groups. Survival analyzed utilizing Kaplan-Meier curves via Cox regression. 200 among received combined whereas remaining 336 alone. With PFS analysis, numbers reduced 176 therapy group 250 group. without PSM, OS consistently significantly better former than latter In Barcelona Clinic Liver Cancer (BCLC) stage B or C, demonstrated higher treated For patients, longer group, before after PSM [hazard ratio (HR), 0.563; 95% CI: 0.360-0.879; P = 0.012, HR, 0.613; 0.382-0.985; 0.043]. However, no statistical difference observed groups for C (HR, 0.673; 0.395-1.146; 0.145). Our data suggested that OS, has sustained benefits both But PFS, could not be persistently by current datasets.

Language: Английский

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Identification of CD8+ T-cell exhaustion signatures for prognosis in HBV-related hepatocellular carcinoma patients by integrated analysis of single-cell and bulk RNA-sequencing

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 10, 2024

Abstract Background HBV infection is the leading risk factor for HCC. has been confirmed to be associated with exhaustion status of CD8 + T cells and immunotherapeutic efficacy in In this study, we aimed investigate prognostic value T-cell signature immunotherapy response patients HBV-related Methods We identified different clusters HCC by single-cell RNA sequencing (scRNA-seq) exhaustion-related genes (TERGs) pseudotime analysis. conducted differential expression analysis LASSO Cox regression detect construct a index (TEI). next combined TEI other clinicopathological factors design nomogram patients. also analysed difference between non-responder responder groups during anti-PD-L1 therapy. addition, investigated how induces lymphocyte through inhibition tyrosine metabolism using gene set enrichment RT‒qPCR. Results A (TEI) was established 5 TERGs (EEF1E1, GAGE1, CHORDC1, IKBIP MAGOH). An AFP level > 500 ng, vascular invasion, histologic grade (G3-G4), advanced TNM stage poor five-year prognosis were related higher score, while lower score. Among those receiving therapy, responders had TEIs than non-responders did. The serves as an independent HCC, incorporating TEI, stage, invasion exhibited excellent predictive RT‒qPCR revealed that among metabolism-associated genes, TAT (tyrosine aminotransferase) HGD (homogentisate 1,2 dioxygenase) expressed at levels HBV-HCC non-HBV Conclusion Generally, novel model comprehensively analysing progression exhaustion, which shows promise predicting clinical potential

Language: Английский

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Advances in Targeted Drug Resistance Associated with Dysregulation of Lipid Metabolism in Hepatocellular Carcinoma

Journal of Hepatocellular Carcinoma, Journal Year: 2024, Volume and Issue: Volume 11, P. 113 - 129

Published: Jan. 1, 2024

Abstract: Hepatocellular carcinoma is the prevailing malignant neoplasm affecting liver, often diagnosed at an advanced stage and associated with unfavorable overall prognosis. Sorafenib Lenvatinib have emerged as first-line therapeutic drugs for hepatocellular carcinoma, improving prognosis these patients. Nevertheless, issue of tyrosine kinase inhibitor (TKI) resistance poses a substantial obstacle in management carcinoma. The pathogenesis advancement exhibit close association metabolic reprogramming, yet attention given to lipid metabolism dysregulation development remains relatively restricted. This review summarizes potential significance research progress dysfunction Targeting holds promising effective strategy overcome drug future. Keywords: metabolism, sorafenib, lenvatinib, targeted

Language: Английский

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Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Metabolites, Journal Year: 2024, Volume and Issue: 14(6), P. 325 - 325

Published: June 8, 2024

Epigenetic and metabolic reprogramming alterations are two important features of tumors, their reversible, spatial, temporal regulation is a distinctive hallmark carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, new entry point for tumor therapy. Moreover, drives hepatocellular carcinoma (HCC) initiation progression, highlighting significance metabolism in this disease. Exploring inter-regulatory relationship between epigenetic modification has become one hot directions current research. As viral etiologies have given way to dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it urgent that complex molecular pathways linking them hepatocarcinogenesis be explored. However, how aberrant crosstalk modifications affects MASLD-induced HCC lacks comprehensive understanding. A better understanding linkages necessary improve treatment strategies. For reason, review examines interwoven landscape carcinogenesis context focusing regulating development interactions while also updating advances modification-based therapeutic drugs HCC.

Language: Английский

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Metabolic reprogramming in hepatocellular carcinoma: a bibliometric and visualized study from 2011 to 2023

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 16, 2024

Metabolic reprogramming has been found to be a typical feature of tumors. Hepatocellular carcinoma (HCC), cancer with high morbidity and mortality, extensively studied for its metabolic reprogramming-related mechanisms. Our study aims identify the hotspots frontiers research in HCC provide guidance future scientific decision-making metabolism. Relevant studies on were derived from Web Science Core Collection (WoSCC) database up until November 2023. The bibliometrix tools R used scientometric analysis visualization. From 2011 2023, total 575 publications obtained WoSCC that met established criteria. These involved 3,904 researchers 948 organizations 37 countries, an average annual growth rate 39.11% research. published 233 journals, Cancers (n = 29) ranking first, followed by Frontiers Oncology 20) International Journal Molecular Sciences 19). top ten journals accounted 26% studies. most prolific authors Wang J 14), Li Y 12), Liu 12). country is China, United States, Italy, France. Fudan University had largest percentage results 15.48% 89). Ally A's paper Cell citations. A 1,204 keywords analyzed, trend themes such as "glycolysis," "tumor microenvironment," "Warburg effect," "mitochondria," "hypoxia ," etc. Co-occurrence network cluster revealed relationships between keywords, authors, publications, journals. Moreover, close collaboration countries this field was elucidated. This bibliometric visual delves into related 2012 elucidating characteristics field, which gradually moved away single glycolipid metabolism integration overall body, pointing out topics, dynamics interaction tumor microenvironment will direction research, provides blueprints inspirations prevention treatment programs field. Systematic Review Registration: [https://www.bibliometrix.org].

Language: Английский

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Proteomic profiling of advanced hepatocellular carcinoma identifies predictive signatures of response to treatments

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Abstract Purpose Hepatocellular carcinoma (HCC) is the most common form of liver cancer with a bad prognosis in case advanced HCC, only eligible for palliative systemic therapies. After decade exclusive sorafenib monotherapy, response rate <10%, advent immunotherapies represents revolution HCC. The combination atezolizumab/bevacizumab recommended as first-line treatment, around 30%. However, there are currently no predictive factors to these treatment options. Experimental Design We profiled, by high-resolution mass spectrometry-based proteomics combined machine learning analysis, selected cohort fixed biopsies grouped subjects according their objective treatments, corresponded tumor regression vs progression at 4 months after treatment. Results generated proteome database 50 HCC samples. compared relative protein abundance between tumoral and non-tumoral tissues from patients treated. clear distinction two groups each based on deregulation 141 or 87 respectively. These specific proteomic signatures were sufficient predict revealed biological pathways involved treatment’s resistance. Particularly, we validated shift cell metabolism an immunosuppressive environment resistance combination. Conclusions performed in-depth analysis quantitative data giving ability optimize patient management.

Language: Английский

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Serum proteomic and metabolomic profiling of hepatocellular carcinoma patients co-infected with Clonorchis sinensis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Clonorchis sinensis (C. sinensis) infection is a significant risk factor for hepatocellular carcinoma (HCC), yet its underlying mechanisms remain poorly understood. This study aimed to investigate the impact of C. on serum proteomic and metabolomic profiling HCC patients, focusing potential mechanisms. A retrospective clinical analysis was conducted 1121 comparing those with without infection. The influence proteome metabolome in further assessed. correlated younger age at cancer onset, male predominance, advanced stage, liver cirrhosis, microvascular invasion patients. It also associated shorter overall survival (OS) recurrence-free (RFS). levels blood lipids (e.g., APO-A, HDL-C, TG) were significantly altered after Proteomic analyses revealed metabolic reprogramming caused by sinensis, excessive depletion argininosuccinate synthase (ASS) D-glucose as factors sinensis-associated malignancy. Key molecules ILF2, CNN2, OLFM4, NOTCH3, LysoPA implicated progression. Furthermore, triggered inflammation, insulin resistance, pro-tumor immune escape, exacerbated complication degenerative diseases. not only provides compelling evidence elucidating sinensis-mediated development but identifies therapeutic targets patients co-infected sinensis.

Language: Английский

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