Refining Prognosis and Treatment Strategies Beyond the Barcelona Clinic Liver Cancer Stage in Hepatocellular Carcinoma with Lung Metastases: A Multicenter Cohort Study.

Lung metastasis is the most common site of extrahepatic spread in hepatocellular carcinoma (HCC) and is associated with significantly poorer outcomes. Current guidelines classify these patients as Barcelona Clinic Liver Cancer (BCLC) stage C, recommending systemic therapy alone. However, this one-size-fits-all approach may overlook potential benefits in selected patients.

ISG15 deficiency in hepatic stellate cells promotes TGFβ2-induced liver fibrosis by counteracting CREB1 ISGylation.

Background: Interferon (IFN)-stimulated gene 15 (ISG15) is a downstream molecule of the IFN pathways central to many cellular processes. ISG15 mainly exerts its function through a post-translational modification process known as ISGylation.

Objective: In this study, the role of ISG15 in the activation of hepatic stellate cells (HSCs) and liver fibrosis was examined.

Exon Skipping of Ste20-Like Kinase Enhances Glycolysis and Tumor Progression by Activating Enolase 1-Mediated Phosphoenolpyruvate Production.

RNA splicing is frequently dysregulated in tumors. Aberrant RNA splicing can alter tumor metabolism, highlighting the need to elucidate the alternative splicing events that shape the metabolic landscape. In this study, we identified exon skipping in Ste20-like kinase (SLK) that results in a variant isoform (SLKv), which promotes glycolysis in tumor cells.

Targeting Aurora kinase B regulates cholesterol metabolism and enhances chemoimmunotherapy in cholangiocarcinoma.

Background: Cholangiocarcinoma (CCA) is a highly lethal malignant tumour with increasing incidence. Current therapies exhibit limited benefits, which urgently demand the identification of novel therapeutic targets.

Objective: We aimed to identify potential therapeutic targets for CCA and broaden current therapies.

NEK7-induced phosphorylation of EGFR on serine 1070 drives the acquired lenvatinib resistance in hepatocellular carcinoma.

Background And Aims: Lenvatinib is recognized as a first-line therapy for inoperable hepatocellular carcinoma (HCC) patients. Growing evidence indicates that lenvatinib resistance can be acquired in HCC cells via kinase rewiring.

Approach And Results: We established acquired lenvatinib-resistant organoids and HCC cell lines.

Riplet promotes lipid metabolism changes associated with CD8 T cell exhaustion and anti-PD-1 resistance in hepatocellular carcinoma.

The overall response rate to immunotherapy is modest in hepatocellular carcinoma (HCC), and immunotherapy resistance mechanisms are incompletely understood. We report that the E3 ubiquitin ligase is universally silenced by promoter hypermethylation in HCC. Loss of modulates fatty acid metabolism to promote terminal exhaustion of CD8 T cells.

Neutrophil Spatiotemporal Regulatory Networks: Dual Roles in Tumor Growth Regulation and Metastasis.

Neutrophils, accounting for 50-70% of circulating leukocytes, exhibit remarkable plasticity in tumor biology. Depending on tumor type and microenvironmental cues, they can exert either anti-tumor or pro-tumor effects. During tumor initiation, neutrophils exposed to chronic inflammation secrete cytokines and oncogenic microRNAs that promote genomic instability and malignant transformation.

Toripalimab plus bevacizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma (HEPATORCH): a randomised, open-label, phase 3 trial.

Background: Although several PD-1 or PD-L1 inhibitors combined with antiangiogenic agents have been approved as first-line treatment of advanced hepatocellular carcinoma, treatment needs remain unmet given the high incidence and mortality of hepatocellular carcinoma and due to factors such as regional approval status, medical insurance restrictions, and cost considerations. In this phase 3 HEPATORCH study, we aimed to compare the efficacy and safety of toripalimab plus bevacizumab versus sorafenib in patients with previously untreated advanced hepatocellular carcinoma.

Methods: We did a randomised, open-label, phase 3 study in 57 hospitals across mainland China, Taiwan, and Singapore.

mA-Mediated TMCO3 Promotes Hepatocellular Carcinoma Progression by Facilitating the Membrane Translocation and Activation of AKT.

The transmembrane and coiled-coil domains 3 (TMCO3) are highly expressed in many tumors. However, the underlying mechanisms governing the way in which TMCO3 affects the progression of hepatocellular carcinoma (HCC) remain unclear. This study screens out the molecule TMCO3 with high N6-methyladenosine (mA) modification level in tumor samples compared to the adjacent non-cancerous tissues of three pairs of HCC patients through Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and RNA sequencing (RNA-seq).

E-twenty-six-specific sequence variant 5 (ETV5) facilitates hepatocellular carcinoma progression and metastasis through enhancing polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC)-mediated immunosuppression.

Background: Despite the success of immune checkpoint blockade, a lack of understanding of the hepatocellular carcinoma (HCC) immune microenvironment impedes its development.

Objective: We aim to elucidate the essential function of E-twenty-six-specific sequence variant 5 (ETV5) in regulating the immune microenvironment in HCC.

Design: Humanised mouse models, murine orthotopic models and diethylnitrosamine/carbon tetrachloride (DEN/CCl)-induced HCC models were used to examine the function of ETV5.

Cancer stem cells and niches: challenges in immunotherapy resistance.

Cancer stem cells (CSCs) are central to tumor progression, metastasis, immune evasion, and therapeutic resistance. Characterized by remarkable self-renewal and adaptability, CSCs can transition dynamically between stem-like and differentiated states in response to external stimuli, a process termed "CSC plasticity." This adaptability underpins their resilience to therapies, including immune checkpoint inhibitors and adoptive cell therapies (ACT).

PA2G4 in health and disease: An underestimated multifunctional regulator.

Background: Proliferation-associated protein 2G4 (PA2G4), also known as ErbB3-binding protein 1 (EBP1), is an evolutionarily conserved, ubiquitously expressed, multifunctional factor in health and disease. In recent decades, its role as a sophisticated regulator in a broad range of biological processes has drawn widespread attention from researchers.

Aim Of Review: We introduce the molecular structure, functional modules, and post-translational modifications of PA2G4.

Machine learning models for predicting postoperative peritoneal metastasis after hepatocellular carcinoma rupture: a multicenter cohort study in China.

Background: Peritoneal metastasis (PM) after the rupture of hepatocellular carcinoma (HCC) is a critical issue that negatively affects patient prognosis. Machine learning models have shown great potential in predicting clinical outcomes; however, the optimal model for this specific problem remains unclear.

Methods: Clinical data were collected and analyzed from 522 patients with ruptured HCC who underwent surgery at 7 different medical centers.

Neuroscience of cancer: unraveling the complex interplay between the nervous system, the tumor and the tumor immune microenvironment.

The study of the multifaceted interactions between neuroscience and cancer is an emerging field with significant implications for understanding tumor biology and the innovation in therapeutic approaches. Increasing evidence suggests that neurological functions are connected with tumorigenesis. In particular, the peripheral and central nervous systems, synapse, neurotransmitters, and neurotrophins affect tumor progression and metastasis through various regulatory approaches and the tumor immune microenvironment.

TGM2-mediated histone serotonylation promotes HCC progression via MYC signalling pathway.

Background & Aims: Hepatocellular carcinoma (HCC) is an aggressive malignancy for which there are few effective treatment options. H3Q5ser, a serotonin-based histone modification mediated by transglutaminase 2 (TGM2), affects diverse biological processes, such as neurodevelopment. The role of TGM2-mediated H3Q5ser in HCC progression remains unclear.

Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.

The tumor microenvironment (TME) is involved in cancer initiation and progression. With advances in the TME field, numerous therapeutic approaches, such as antiangiogenic treatment and immune checkpoint inhibitors, have been inspired and developed. Nevertheless, the sophisticated regulatory effects on the biological balance of the TME remain unclear.

Laennec approach for anatomical liver resection assisted by laparoscopy or robotics: a multicenter cohort study.

Introduction: Laennec's capsule serves as a critical anatomical landmark in liver resection. Despite its potential, a lack of large-scale prospective studies limits the widespread use of the Laennec approach for minimally invasive hepatectomy. This multicenter cohort study aimed to compare the outcomes of the traditional and Laennec approaches in minimally invasive anatomical hepatectomy across multiple centers in China.

B cells and tertiary lymphoid structures in tumors: immunity cycle, clinical impact, and therapeutic applications.

Tumorigenesis involves a multifaceted and heterogeneous interplay characterized by perturbations in individual immune surveillance. Tumor-infiltrating lymphocytes, as orchestrators of adaptive immune responses, constitute the principal component of tumor immunity. Over the past decade, the functions of tumor-specific T cells have been extensively elucidated, whereas current understanding and research regarding intratumoral B cells remain inadequate and underexplored.

CKAP4 in hepatocellular carcinoma: competitive RETREG1/FAM134B binding, reticulophagy regulation, and cancer progression.

RETREG1/FAM134B is known for its role as a reticulophagy receptor. Our previous study established that RETREG1 is upregulated in hepatocellular carcinoma (HCC) and contributes to disease progression by activating the AKT signaling pathway. However, the specific mechanisms underlying the elevated expression of RETREG1 in HCC remain unclear.

Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis.

N6-methyladenosine reader YTHDF3-mediated zinc finger protein 41 inhibits hepatocellular carcinoma progression by transcriptional repression of Snail.

Advanced metastasis of hepatocellular carcinoma (HCC) significantly contributes to high death rates among patients. The efficiency of targeted therapies and chemotherapeutic agents shows individual variability. Therefore, there is no effective treatment for advanced HCC.

Nano-encapsulation of drugs to target hepatic stellate cells: Toward precision treatments of liver fibrosis.

Liver fibrosis is characterized by excessive extracellular matrix (ECM) deposition triggered by hepatic stellate cells (HSCs). As central players in fibrosis progression, HSCs are the most important therapeutic targets for antifibrotic therapy. However, owing to the limitations of systemic drug administration, there is still no suitable and effective clinical treatment.