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Background The role of mitochondrial dynamics, encompassing fission, fusion, and mitophagy, in cancer progression has been extensively studied. However, the specific impact of mitochondrial dynamics on hepatocellular carcinoma (HCC) is still under investigation. Methods In this study, mitochondrial dynamic genes were obtained from the MitoCarta 3.0 database, and gene expression data were collected from The Cancer Genome Atlas (TCGA) database. Based on the expression of these dynamic genes and differentially expressed genes (DEGs), patients were stratified into two clusters. Subsequently, a prognostic model was constructed using univariate COX regression and the least absolute shrinkage and selection operator (LASSO) regression, and the prognostic signature was evaluated. We analyzed the interaction between these model genes and dynamic genes to identify hub genes and reveal mitochondrial status. Furthermore, we assessed immune infiltration, tumor mutational burden (TMB), tumor stemness indices (TSI), and the response to immune checkpoint block (ICB) therapy using the TIDE algorithm and risk scores. Additionally, transmission electron microscopy (TEM), hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC), western blotting (WB), and immunofluorescence (IF) were conducted to afford detailed visualization of the morphology of the mitochondria and the expression patterns of fission-associated proteins. Results Patients in Cluster 2 exhibited heightened mitochondrial fission and had a worse prognosis. The up-regulated dynamic genes in Cluster 2 were identified as fission genes. GO/KEGG analyses reconfirmed the connection of Cluster 2 to augmented mitochondrial fission activities. Subsequently, a ten-gene prognostic signature based on the differentially expressed genes between the two clusters was generated, with all ten genes being up-regulated in the high-risk group. Moreover, the potential links between these ten signature genes and mitochondrial dynamics were explored, suggesting their involvement in mediating mitochondrial fission through interaction with MTFR2. Further investigation revealed that the high-risk group had an unfavorable prognosis, with a higher mutation frequency of TP53, increased immune checkpoint expression, a higher TIS score, and a lower TIDE score. The mitochondrial imbalance characterized by increased fission and upregulated MTFR2 and DNM1L expression was substantiated in both HCC specimens and cell lines. Conclusions In conclusion, we developed a novel MTFR2-related prognostic signature comprising ten mitochondrial dynamics genes. These genes play crucial roles in mitochondrial fission and have the potential to serve as important predictors and therapeutic targets for HCC.

Metabolic-associated fatty liver disease (MAFLD) is a growing global health concern, particularly among women of childbearing age (WCBA). We aimed to analyze the global burden of MAFLD among WCBA from 1990 to 2021 and project trends to 2040. Data on incidence, prevalence, deaths, and disability-adjusted life years (DALYs) were extracted from the Global Burden of Disease Study 2021. Joinpoint regression and decomposition analysis were used to assess historical trends, and Bayesian Age-Period-Cohort (BAPC) modeling projected future burdens. From 1990 to 2021, the age-standardized rate (ASR) of MAFLD incidence and prevalence among WCBA increased globally (EAPC = 0.76 and 0.71, respectively). China showed declining trends in deaths (EAPC = -2.63) and DALYs (EAPC = -2.62). By 2040, BAPC modeling predicts a continued rise in global incidence and prevalence, with regional disparities in mortality. Population growth was the primary driver of the global increase in MAFLD incidence, accounting for 63.38% of the rise. MAFLD imposes a significant burden on WCBA globally, with socioeconomic disparities driving regional variations. Targeted interventions addressing obesogenic environments and healthcare inequities are urgently needed.

Neutrophil extracellular traps (NETs) play important roles in hepatic ischemic reperfusion injury (IRI) and acute rejection (AR)-induced immune responses to inflammation. After liver transplantation, HMGB1, an inflammatory mediator, contributes to the development of AR. Even though studies have found that HMGB1 can promote NET formation, the correlation between NETs and HMGB1 in the development of AR following liver transplantation has not been elucidated. In this study, levels of serum NETs were significantly elevated in patients after liver transplantation. Moreover, we found that circulating levels of NETs were negatively correlated with liver function. In addition, liver transplantation and elevated extracellular HMGB1 promoted NET formation. The HMGB1/TLR-4/MAPK signaling pathway, which is initiated by HMGB1, participates in NET processes. Moreover, in the liver, Kupffer cells were found to be the main cells secreting HMGB1. NETs induced Kupffer cell M1 polarization and decreased the intracellular translocation of HMGB1 by inhibiting DNase-1. Additionally, co-treatment with TAK-242 (a TLR-4 inhibitor) and rapamycin more effectively alleviated the damaging effects of AR following liver transplantation than either drug alone.

The transcriptional coactivator with PDZ binding motif (TAZ) has been reported to be one of the nuclear effectors of Hippo‐related pathways. TAZ is expressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in hepatocellular carcinoma (HCC). In the current study, we show that TAZ regulates cellular proliferation and epithelial–mesenchymal transition (EMT) of HCC. TAZ is overexpressed in HCC tissues and cell lines and upregulation of TAZ correlates with a lower overall survival rate of HCC patients after hepatic resection. TAZ knockdown results in inhibition of cancer cell proliferation through decreases in expression of stem cell markers (OCT4, Nanog, and SOX2). Reduction in HCC cell migration and invasion is also evident through reversal of EMT by increases E‐cadherin expression, decreases in N‐cadherin, vimentin, Snail, and Slug expression, and suppression of MMP‐2 and MMP‐9 expression. In a xenograft tumorigenicity model, TAZ knockdown could effectively inhibit tumor growth and metastasis through reversal of the EMT pathway. In conclusion, TAZ is associated with the proliferation and invasiveness of HCC cells, and the TAZ gene may contribute to a novel therapeutic approach against HCC. The transcriptional coactivator with PDZ binding motif (TAZ) is expressed in many primary tumors and could regulate many biological processes. In this study, TAZ is overexpressed in HCC tissues and up‐regulation of TAZ correlates with low over‐all survival rate of HCC patients after hepatic resection. TAZ is associated with the proliferation and invasiveness of HCC cells, and TAZ gene may contribute to a novel therapeutic approach against HCC.

Multiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting and controlling the advancement of tumors. While there is an abundance of information highlighting the importance of TLS in different cancer types, their prognostic significance specifically in hepatocellular carcinoma (HCC) cancers remains unclear. Thus, this meta-analysis aimed to explore the prognostic relevance of TLS in HCC. We conducted a thorough search across four databases, namely Web of Science, PubMed, Embase, and the Cochrane Library, to identify pertinent studies. The search utilized the keywords \"tertiary lymphoid structures\" and \"hepatocellular carcinoma.\" The primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HR). Six studies were incorporated into the analysis. Among them, four studies, encompassing 6 datasets and involving 1490 patients, and three studies, comprising 5 datasets and involving 656 patients, respectively, investigated the correlation between intratumoral and peritumoral TLSs and the prognosis in HCC patients. The meta-analysis revealed that the presence of intratumoral TLSs is linked to longer RFS and reduced early recurrence (HR, 0.60; 95% CI, 0.50-0.67; p <0.001 and HR, 0.49; 95% CI, 0.36-0.65; p <0.001, respectively). However, no significant association was observed with OS and late recurrence. Sensitivity analysis demonstrated the robustness of these findings, and heterogeneities were minimal. Additionally, the meta-analysis did not detect a relationship between peritumoral TLSs and OS or RFS in HCC patients. The presence of intratumoral TLSs is correlated with better RFS and reduced early recurrence in HCC patients. Further investigation is warranted to elucidate the roles of peritumoral TLSs in the prognosis of HCC patients. https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023466793.

This pilot study aims to evaluate the technical feasibility, safety profile, and preliminary efficacy of Tepoxin, a thermosensitive hydrogel, combined with pirarubicin via transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC), providing foundational data for future larger-scale trials. This is a single-center, retrospective, single-arm pilot study including 7 HCC patients who received Tepoxin combined with pirarubicin TACE between 2023 and 2025. Inclusion criteria were: confirmed HCC by imaging or pathology, Child-Pugh A-B liver function, ECOG performance status ≤ 2, and no severe comorbidities. The procedure involved selective hepatic artery catheterization to deliver pirarubicin-loaded hydrogel for embolization. Primary endpoints were procedure success rate, adverse events, tumor response (evaluated by changes in the maximum tumor diameter and mRECIST criteria for PR/SD/PD), and disease control rate (DCR). Follow-up was conducted for at least 4-6 weeks for preliminary imaging assessment. All 7 patients completed the procedure without failure or discontinuation. Tumor response was assessable in all patients: 2 achieved partial response (PR), 4 had stable disease (SD), and 1 had progression (PD). The objective response rate (ORR) was 28.6% (2/7), and the disease control rate (DCR) was 85.7% (6/7). Adverse events were mild, including fever, abdominal pain, and nausea/vomiting (grade 1-2), with no severe toxicity (grade ≥3) or treatment interruption. Mild liver function fluctuations were observed in some patients, which recovered to baseline. Tepoxin combined with pirarubicin TACE is technically feasible and well-tolerated in HCC patients, showing early anti-tumor activity. Larger, well-designed studies are needed to confirm its efficacy and safety.

Purpose Prealbumin, a marker of nutritional and inflammatory status, has shown prognostic value in various malignancies. This study aimed to evaluate the prognostic significance of preoperative serum prealbumin levels in gallbladder cancer (GBC) patients undergoing radical resection. Methods A multicenter retrospective study included 210 patients who underwent radical GBC resection. The optimal prealbumin cutoff (221 mg/L) was identified via ROC analysis. Patients were stratified into high and low prealbumin groups. Kaplan–Meier and Cox regression analyses were used to assess the association between prealbumin levels and overall survival (OS) and recurrence-free survival (RFS). Results Patients with low prealbumin levels ( n  = 120) had 1-year OS and RFS rates of 65% and 44.1%, respectively. In contrast, high prealbumin patients ( n  = 90) showed significantly better OS (96.6%) and RFS (90%) ( p  < 0.001). Multivariate analysis confirmed prealbumin as an independent predictor of OS (HR = 0.179, 95% CI: 0.052–0.622, p  = 0.007) and RFS (HR = 0.220, 95% CI: 0.102–0.474, p  < 0.001). A combined model of prealbumin and hemoglobin improved predictive accuracy for OS (AUC = 0.762) and RFS (AUC = 0.771). Conclusion Preoperative serum prealbumin is an independent prognostic biomarker in GBC patients undergoing radical resection. Combining prealbumin with hemoglobin enhances prediction of postoperative survival.

The tumor margin of hepatocellular carcinoma (HCC) is a critical zone where cancer cells invade the surrounding stroma, exhibiting unique and more invasive metabolic and migratory features compared to the tumor center, driving tumor expansion beyond the primary lesion. Studies have shown that at this critical interface, HCC cells primarily rely on fatty acid oxidation to meet their energy demands, although the underlying mechanisms remain unclear. This study demonstrates that activated hepatic stellate cells (HSCs) at the tumor margin play a pivotal role in sustaining the metabolic needs of HCC cells. Specifically, it is discovered that mitochondrial fission regulator 2 (MTFR2) in HSCs interacts with dynamin‐related protein 1 (DRP1, a known mitochondrial fission machinery), preventing its lysosomal degradation, which in turn promotes mitochondrial fission. This MTFR2‐driven mitochondrial fission enhances the transfer of both fatty acids and mitochondria to HCC cells, supplying essential metabolic substrates and reinforcing the mitochondrial machinery critical for tumor growth. The findings suggest that targeting MTFR2‐driven mitochondrial fission may offer a novel therapeutic avenue for interfering with the metabolic crosstalk between tumor cells and the stromal niche. In the tumor margin of hepatocellular carcinoma (HCC), activated hepatic stellate cells upregulate MTFR2, initiating inhibiting DRP1 degradation and mitochondrial fission. This enhances mitochondrial availability and facilitates FAs synthesis via ACC1. Additionally, fission promotes RAC1‐mediated cytoskeletal remodeling and Miro1‐mediated mitochondrial transport, enabling HCC cells to utilize transferred resources for increased fatty acid oxidation and ATP production.

Background Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors, with a high rate of recurrence worldwide. This study aimed to investigate the mechanism underlying the progression of HCC and to identify recurrence-related biomarkers. Methods We first analyzed 132 HCC patients with paired tumor and adjacent normal tissue samples from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). The expression profiles and clinical information of 372 HCC patients from The Cancer Genome Atlas (TCGA) database were next analyzed to further validate the DEGs, construct competing endogenous RNA (ceRNA) networks and discover the prognostic genes associated with recurrence. Finally, several recurrence-related genes were evaluated in two external cohorts, consisting of fifty-two and forty-nine HCC patients, respectively. Results With the comprehensive strategies of data mining, two potential interactive ceRNA networks were constructed based on the competitive relationships of the ceRNA hypothesis. The ‘upregulated’ ceRNA network consists of 6 upregulated lncRNAs, 3 downregulated miRNAs and 5 upregulated mRNAs, and the ‘downregulated’ network includes 4 downregulated lncRNAs, 12 upregulated miRNAs and 67 downregulated mRNAs. Survival analysis of the genes in the ceRNA networks demonstrated that 20 mRNAs were significantly associated with recurrence-free survival (RFS). Based on the prognostic mRNAs, a four-gene signature (ADH4, DNASE1L3, HGFAC and MELK) was established with the least absolute shrinkage and selection operator (LASSO) algorithm to predict the RFS of HCC patients, the performance of which was evaluated by receiver operating characteristic curves. The signature was also validated in two external cohort and displayed effective discrimination and prediction for the RFS of HCC patients. Conclusions In conclusion, the present study elucidated the underlying mechanisms of tumorigenesis and progression, provided two visualized ceRNA networks and successfully identified several potential biomarkers for HCC recurrence prediction and targeted therapies.