Tumor cell-derived IL-23 promotes hepatocellular carcinoma progression via an autocrine IL-23/EGFR/AKT signaling axis.

Semantic inductive graph-based diagnostics: A category-aware NLP-GCN framework for robust cancer detection via cfDNA end-motif and fragmentation analysis.

Delivery of a ZBP1 agonist enhances radiotherapy-induced antitumour immunity in hepatocellular carcinoma.

DTMB attenuates hepatic inflammation and lipid dysregulation via PPAR-γ modulation in diet-induced steatohepatitis.

Dual-adjuvanted GPC3 mRNA vaccine delivered by lipid nanoparticles for hepatocellular carcinoma immunotherapy.

NIPBL::NACC1 fusion hepatic tumor: report of a case

Targeted Antagonistic ATP-Gated P2X7 Receptor Inhibits the Migration and Invasion of Hepatocellular Carcinoma Cells.

KLF16 transcriptionally activates HSPB1 to participate in the sorafenib resistance of hepatocellular carcinoma by driving ferroptosis resistance.

Hepatocellular carcinoma (HCC) is a highly immunosuppressive cancer with limited treatment options and poor prognosis. Neutrophils, as prominent immune cells in the tumour microenvironment, critically shape disease progression and treatment response. Here, we aimed to identify pivotal neutrophil subsets driving HCC progression. Neutrophil-specific marker genes were identified through single-cell RNA sequencing (scRNA-seq) analyses. The clinical significance of neutrophils with triggering receptor expressed on myeloid cells-1 (TREM1) positive was assessed in HCC patient cohort by immunofluorescence staining. The immune landscape of HCC and the functional phenotype of TREM1+ neutrophils were further characterised using cytometry by time-of-flight (CyTOF). scRNA-seq analyses revealed that TREM1 was mainly expressed in intratumoural neutrophils within the HCC microenvironment. A high abundance of intratumoural TREM1+ neutrophils was significantly associated with poor prognosis in HCC patients. CyTOF profiling demonstrated that HCC tumours enriched with TREM1+ neutrophils exhibited CD8+ T-cell exclusion and increased infiltration of immunosuppressive macrophages. Moreover, TREM1+ neutrophils exhibited an immunosuppressive functional state. Pharmacological inhibition of TREM1 by VJDT enhanced the therapeutic efficacy of anti-PD-1 antibody in HCC preclinical models. TREM1 is mainly expressed in neutrophils in HCC and drives the immunosuppressive reprogramming of neutrophils and tumour microenvironment. Infiltration of TREM1+ neutrophils correlates with unfavourable clinical outcomes in HCC. Targeting TREM1 may augment the efficacy of anti-PD-1 therapy in HCC.

Hepatocellular carcinoma (HCC) is characterized by profound metabolic reprogramming and an immunosuppressive tumor immune microenvironment (TIME). Lactate accumulation has recently been implicated in protein lactylation and tumor progression, but its role in reshaping the TIME in HCC remains incompletely understood. To investigate how lactate-related metabolic reprogramming influences global protein lactylation and the TIME in HCC. We integrated high-throughput RNA sequencing, construction of a lactate metabolic process activity (LMPA) model, molecular subtyping, survival analysis and single-cell RNA sequencing to characterize lactate-associated alterations in HCC. Tissue microarrays and in vitro functional assays were used to validate key findings. Elevated expression of lactate dehydrogenase A (LDHA), a core enzyme in lactate metabolism, was significantly associated with altered transcriptional profiles, unfavorable survival and changes in TIME composition in patients with HCC. In vitro, LDHA overexpression promoted HCC cell proliferation, migration and invasion. Patients with high LMPA exhibited significantly poorer prognosis and distinct immune infiltration patterns, including altered proportions of B cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells. Single-cell RNA sequencing further revealed heterogeneous LMPA patterns across cell populations and increased global protein lactylation, particularly in immune cells. In addition, LMPA-based molecular subtypes were closely associated with lactylation-related features. LDHA expression, HDAC2 expression and metastasis were identified as significant prognostic factors. Lactate-related metabolic reprogramming may enhance global protein lactylation and remodel the TIME in HCC, thereby promoting tumor progression. These findings highlight the potential of targeting lactate metabolism and lactylation-associated pathways as novel therapeutic strategies for HCC.

Hepatocellular carcinoma (HCC) disproportionately affects racial/ethnic minorities and socioeconomically disadvantaged populations. We assessed how race/ethnicity, insurance type, and neighborhood deprivation relate to HCC stage at diagnosis, treatment receipt, and survival in an integrated health care system. We conducted a retrospective cohort study of 3441 adults diagnosed with HCC between 2006 and 2019 within Kaiser Permanente Northern California. Multivariable Cox regression models evaluated associations between race/ethnicity, insurance type, neighborhood deprivation index (NDI), and key outcomes: advanced-stage HCC (Barcelona Clinic Liver Cancer stage C), receipt of curative or any treatment, and 5-year survival. Among patients with HCC (median age 65y; 75.0% male), 42.6% were White, 8.4% Black, 21.9% Hispanic/Latinx, and 24.6% Asian/Pacific Islander (API). Advanced-stage HCC was more common among Black (32.6%) and although HCC treated patterns did not differ by race/ethnicity, insurance type, or neighborhood deprivation index, API patients had lower odds of presenting with advanced-stage HCC (adjusted odds ratio, 0.62, 95% CI 0.48-0.81) and had better 5-year survival (adjusted hazard ratio 0.74; 95% CI 0.64-0.87) compared with White patients. Residence in a more socioeconomically deprived neighborhood was associated with worse 5-year survival (adjusted hazard ratio, 1.20; 95% CI, 1.01-1.41) relative to residence in less deprived areas. These findings highlight persistent inequities in HCC stage at diagnosis and survival, with API patients experiencing more favorable outcomes and individuals from socioeconomically deprived neighborhoods facing worse long-term survival. Efforts to reduce structural barriers and improve early detection are needed to narrow these disparities.

Targeting the Polycomb repressive complexes in hepatocellular carcinoma: A comprehensive and updated analysis of mechanistic insights and clinical application.

Background Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with a poor survival rate despite advances in therapy. Metabolic reprogramming, particularly involving lactate transport, plays a critical role in HCC progression. Monocarboxylate transporter 4 (MCT4) is a key lactate exporter often overexpressed in cancers, yet its precise role in HCC pathogenesis and immune modulation remains incompletely defined. Methods We integrated bioinformatic analyses of multiple datasets (TCGA-LIHC, GSE46408, GSE36411) with experimental validation in HCC cell lines (Huh7, MHCC97-H) and a murine xenograft model. Functional assays including wound healing, Transwell invasion, Western blot, and flow cytometry were employed. Immune cell infiltration and polarization were analyzed via CIBERSORT and single-cell RNA sequencing data (GSE282701). Results MCT4 was identified as a prognostic hub gene among lactate metabolism-related genes (LMRGs) and was significantly upregulated in HCC tissues, correlating with advanced tumor stage and poor survival. Gene Set Enrichment Analysis (GSEA) revealed a strong association between MCT4 expression and matrix metalloproteinase (MMP) pathways. In vitro , MCT4 knockdown downregulated MMP1, MMP2, and MMP9 expression and suppressed HCC cell migration and invasion. Furthermore, high MCT4 expression was linked to an immunosuppressive tumor microenvironment characterized by M2 macrophage polarization. In vivo , MCT4 knockdown inhibited tumor growth and reduced infiltration of CD206 + M2 macrophages. Conclusions Our findings demonstrate that MCT4 drives HCC progression through two complementary mechanisms: enhancing MMP-mediated invasion and metastasis, and promoting immunosuppressive M2 macrophage polarization. These results nominate MCT4 as a promising therapeutic target for restoring antitumor immunity and inhibiting metastasis in HCC.

The present study aimed to investigate the effects of microRNA (miR)‑5590‑3p on the biological functions of hepatocellular carcinoma (HCC) cells through the homeobox B2 (HOXB2)/MYC axis. The expression levels of miR‑5590‑3p, HOXB2 and MYC were measured in HCC tissues and cell lines, and the relationships between miR‑5590‑3p, HOXB2, and the clinicopathological characteristics and prognosis of patients with HCC were analyzed. The Cell Counting Kit‑8 assay assessed cell proliferation, flow cytometry measured apoptosis rate, and the Transwell and wound healing assays evaluated the invasive and migratory abilities of cells. The targeting interactions between miR‑5590‑3p and HOXB2, and between HOXB2 and MYC were assessed. In addition, a subcutaneous HCC xenograft model was established to assess the effects of miR‑5590‑3p on tumor growth. The results revealed that miR‑5590‑3p expression was downregulated in HCC tissues and cells, whereas HOXB2 and MYC expression were upregulated. Notably, low miR‑5590‑3p expression and high HOXB2 expression were both associated with a poor prognosis in patients with HCC. miR‑5590‑3p directly targeted and suppressed HOXB2, whereas HOXB2 promoted MYC transcription. Furthermore, downregulation of miR‑5590‑3p enhanced the invasion, migration and proliferation of Huh7 cells, and reduced their apoptotic rate. By contrast, miR‑5590‑3p overexpression or HOXB2 silencing decreased invasion, migration and proliferation, while increasing apoptosis. Moreover, HOXB2 overexpression reversed the inhibitory effect of miR‑5590‑3p upregulation on HCC cell proliferation. HOXB2 appeared to promote Huh7 cell proliferation and motility through MYC transcriptional activation, whereas miR‑5590‑3p overexpression suppressed tumor growth in vivo. In conclusion, miR‑5590‑3p may inhibit HCC cell proliferation and motility, and induce apoptosis by targeting HOXB2 and suppressing MYC transcription.

This study sought to investigate the impact of MAPK12 on immune evasion in hepatocellular carcinoma (HCC) by modulating PD-L1 expression through the PI3K/AKT/mTOR pathway. Using GEPIA, Kaplan-Meier plotter, and TIMER databases, MAPK12 expression in HCC and its prognostic value were analyzed. MAPK12 expression was knocked down in HCC cells using shRNAs, and cell proliferation, migration, invasion, and EMT were evaluated. CD8+ T cells were co-cultured with HCC cells. An orthotopic HCC mouse model was established to observe tumor growth, survival duration, CD8+ T cell infiltration, and levels of cytokines and effector molecules. MAPK12 expression was higher in HCC tissues and cell lines. HCC patients with high MAPK12 exhibited shorter overall survival. MAPK12 knockdown reduced HCC cell growth and EMT progression, suppressed PD-L1 expression, and enhanced CD8+ T cell killing activity. MAPK12 deficiency suppressed the PI3K/Akt/mTOR pathway activation, while the PI3K activator (740Y-P) reversed PD-L1 downregulation and immune killing effects. The immunosuppressive effect mediated by MAPK12 overexpression was blocked by the PI3K inhibitor LY294002. MAPK12 knockdown restricted tumor growth and extended survival in mice, accompanied by increased CD8+ T cell infiltration. In summary, MAPK12 promotes HCC immune escape by upregulating PD-L1 via the PI3K/Akt/mTOR pathway.

Enhanced Prediction of Hepatitis B Virus-Related Hepatocellular Carcinoma Using Age-Male-Albumin-Bilirubin-Platelet (aMAP) and Liver Stiffness Assessed by Vibration-Controlled Transient Elastography.

6H2L, a novel derivative of bifendate, dually suppresses glycolysis and glutaminolysis in hepatocellular carcinoma via inhibiting YAP stability.

Lipiodol-Based Balloon-Occluded Transcatheter Arterial Chemoembolization Can Be a Curative Treatment Option for Hepatocellular Carcinoma.

A multidimensional strategy for identifying quality markers of Radix ginseng-Schisandra chinensis in the disruption of the inflammation-cancer transformation process of hepatocellular carcinoma based on metabolic regulation and chemical properties.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and often arises in cirrhosis cases. Current surveillance methods, including ultrasonography and α-fetoprotein, have limited sensitivity for early detection. Blood metabolomics may improve HCC risk prediction. We aimed to identify pre-diagnostic plasma metabolites associated with HCC risk and evaluate whether cirrhosis-related metabolites enhance prediction beyond established risk factors in a multiethnic population. We analyzed data from a nested case-control study with pre-diagnostic blood samples in the Multiethnic Cohort, including 240 HCC cases, 151 cirrhosis cases, and individually matched controls. Metabolome-wide association studies and pathway enrichment analyses were performed, followed by feature selection in the cirrhosis samples to construct HCC prediction models. Of 294 metabolites analyzed, 53 were significantly associated with HCC after false discovery rate correction (odds ratios: 0.25-3.93). Pathway analyses highlighted perturbations in lipid and amino acid metabolism. Two cirrhosis-associated metabolites, glutamate and glycochenodeoxycholate, were consistently selected and improved HCC prediction. Adding these metabolites to known risk factors (age, sex, race/ethnicity, study area, BMI, smoking, alcohol consumption, and diabetes) increased the AUC from 0.64 to 0.73 (P < 0.001). Pre-diagnostic metabolomic profiling revealed metabolic alterations linked to HCC risk, emphasizing dysregulated amino acid and bile acid pathways within the cirrhosis context. Glutamate and glycochenodeoxycholate improved HCC risk prediction beyond established factors, supporting biologically plausible links between hepatic metabolic dysfunction and hepatocarcinogenesis. These findings highlight the potential of metabolomic biomarkers to enhance surveillance and risk stratification among patients with cirrhosis.