The heterogeneity in prognostic survival and treatment response of hepatocellular carcinoma (HCC) limits the accurate assessment of HCC-specific mortality. This study aimed to identify potential HCC subtypes through latent class analysis (LCA) to improve HCC-specific mortality prediction and optimize treatment recommendations. We analyzed data from 7746 HCC patients in the Surveillance, Epidemiology, and End Results (SEER) databases, incorporating demographic and clinicopathological information and applying LCA to identify HCC subtypes. Prognostic survival and treatment response across different HCC subtypes were evaluated utilizing Cox proportional hazards regression and competing risks models. The classification was externally validated with data from 6791 patients. Four HCC subtypes (LCAC1-LCAC4) were determined. Compared with LCAC1, both LCAC2 (HR = 1.887, p < .001) and LCAC4 (HR = 1.317, p < .001) were associated with significantly shorter overall survival. LCAC2 had the highest HCC-specific mortality (HR: 2.395, p < .001), followed by LCAC4 (HR: 1.531, p < .001), and LCAC3 (HR: 1.424, p < .001). LCAC3 was associated with the lowest risk of non-HCC-specific mortality (HR: 0.613, p < .001). Surgical treatment, particularly preoperative systemic therapy, significantly improved survival across all HCC subtypes, whereas chemotherapy and radiotherapy had limited efficacy in LCAC1 and LCAC3 patients. External validation corroborated these findings. This study provides a classification system that differentiates HCC-specific mortality, facilitating accurate survival stratification and treatment recommendations, and provides valuable insight for clinical decision-making.

The progression from hepatitis to liver fibrosis (LF) and ultimately to hepatic carcinoma (HCC) represents the advanced stages of various liver diseases. Currently, no universal treatment effectively addresses all three conditions. The Traditional Chinese Medicine formula Xiao-Chai-Hu decoction (XCHD) has shown promise in treating hepatitis, inhibiting LF, and serving as an adjunct therapy for HCC. This study evaluates the efficacy and optimal treatment durations of XCHD in managing these liver diseases using meta-analysis and machine learning techniques.

Registered in the PROSPERO database (CRD42024534445), this meta-analysis systematically searched seven databases, including 54 studies with a total of 5,710 patients. Statistical analysis was performed using Stata 17.0. Five machine learning models-Random Forest (RF), XGBoost, Lasso, Multilayer Perceptron (MLP), and a stacking model combining these algorithms-were employed to analyze the data and predict the time-effect relationships. The optimal durations of XCHD treatment for the liver disease trilogy were subsequently projected.

XCHD significantly improved the primary outcome indicators for hepatitis, liver fibrosis, and HCC. Additionally, XCHD demonstrated a beneficial effect on liver dysfunction caused by these diseases. Machine learning predicted the optimal treatment durations of XCHD as 12 weeks for hepatitis, 20.31 weeks for liver fibrosis, and 12 weeks for HCC.

XCHD is effective in treating the liver disease trilogy, with optimal treatment durations of 12 weeks for hepatitis and HCC, and 20.31 weeks for liver fibrosis. These findings support the potential of XCHD in developing precise clinical strategies for managing liver diseases. This study innovatively integrates meta-analysis with machine learning to determine the optimal treatment durations, providing a novel approach for evidence-based precision medicine in Traditional Chinese Medicine.

Statistical cure, defined as achieving life expectancy comparable with that of disease-free individuals, has not been specifically investigated in hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC), which accounts for more than 50% of the global HCC burden. This study aimed to develop a cure model for HBV-HCC after hepatectomy using matched HBV carriers and the general population as reference groups.

From a Chinese multicenter database, HBV-HCC patients who underwent curative-intent hepatectomy were retrospectively reviewed. Independent prognostic factors were identified through Cox regression. A spline-based cure model was applied using two reference populations: matched Chinese HBV carriers (from Shanghai Center for Disease Control and Prevention) and the general population (from the National Bureau of Statistics).

The study analyzed 740 HBV-HCC patients. The following eight independent risk factors were identified: preoperative high viral load (hazard ratio [HR] 1.27), Child-Pugh grade (HR 1.21 and 1.43), multiple tumors (HR 1.70), tumor size greater than 5.0 cm (HR 1.47), macrovascular invasion (HR 3.33), microvascular invasion (HR 1.25), intraoperative blood transfusion (HR 1.21), and postoperative HBV reactivation (HR 1.89). The overall cure probability was 21.2% versus that for HBV carriers and 11.1% versus that for the general population. Risk stratification identified distinct groups relative to HBV carriers. Low risk (64.2%) showed an initial cure rate of 30.3% and achieved a 95% cure probability by 8.6 years, whereas high risk (10.5%) showed negligible cure probability.

This first HBV-HCC-specific cure model demonstrated that statistical cure is achievable for a subset of patients after hepatectomy. Risk stratification identifies patients with varying cure probabilities, providing valuable guidance for personalized treatment strategies and surveillance protocols.

Exosomes are extracellular vesicles with a diameter ranging from 40 to 160 nm. They are produced by hepatocytes, cholangiocytes, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs) and Kupffer cells in liver tissue. The secretion of exosomes might vary in quantity and composition in reaction to multiple triggers and various stages of disease. They transport various payloads, such as proteins, DNAs, and RNAs, and enable cell interaction to regulate myriad physiological and pathological processes in liver tissue. Long non-coding RNAs (lncRNAs) are a crucial component of exosomes with an excellent capability to regulate multiple cellular activities such as differentiation, development, metabolism, proliferation, apoptosis, and activation. With the advancements in transcriptomic and genomic study methods and database management technology, the functions and mechanisms of exosomal lncRNAs in liver diseases have been well-studied. This article delves into the detailed role of exosomal lncRNAs in liver disease onset and progression, ranging from hepatocellular carcinoma (HCC) to liver fibrosis drug-induced liver damage (DILI) and steatotic liver diseases.

This study aimed to assess prognostic significance of FDG PET/CT parameters in predicting progression-free survival (PFS) and overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab therapy.

We retrospectively enrolled 78 patients with HCC who underwent FDG PET/CT before atezolizumab plus bevacizumab therapy and identified intrahepatic target tumor lesions on pretreatment imaging studies. From PET/CT images, we measured SUVmax, tumor-to-normal liver uptake ratio, metabolic tumor volume, and total lesion glycolysis (TLG) for intrahepatic tumor lesions, as well as SUVmax for extrahepatic metastatic lesions (extrahepatic SUVmax).

In comparisons of PET/CT parameters, patients with progressive disease demonstrated significantly higher TLG values than those achieving complete or partial response ( P < 0.05). In the multivariate survival analysis, TLG independently predicted both PFS ( P = 0.019) and OS ( P = 0.003). Metabolic tumor volume was significantly associated with OS alone ( P = 0.010), and extrahepatic SUVmax was significantly associated with only PFS ( P = 0.045). Patients with high TLG values experienced poorer PFS and OS than those with low TLG values ( P < 0.05).

TLG in intrahepatic HCC lesions was significantly associated with treatment response and served as an independent prognostic factor for PFS and OS. TLG could be a potential imaging biomarker for predicting clinical outcomes in patients with HCC receiving atezolizumab plus bevacizumab therapy.

This study aims to develop and validate a predictive nomogram for early recurrence in hepatocellular carcinoma (HCC), utilizing gadoxetic acid-enhanced MRI and intravoxel incoherent motion (IVIM) imaging to improve preoperative assessment and decision-making.

From March 2018 and June 2022, a total of 245 patients with pathologically confirmed HCC, who underwent preoperative gadoxetic acid-enhanced MRI and IVIM, were retrospectively enrolled from two hospitals. These patients were divided into a training cohort (n = 160) and a validation cohort (n = 85). All patients were followed until death or the last follow-up date, with a minimum follow-up period of two years. Clinical indicators and pathologic information were compared between train cohort and validation cohort. Radiological features and diffusion parameters were compared between recurrence and non-recurrence groups using the chi-square test, Mann-Whitney U test and independent sample t test in training cohort. Univariate and multivariate analyses were performed to identify significant clinical-radiological variables associated with early recurrence in the training cohort. Based on these findings, a predictive nomogram integrating risk factors and diffusion parameters was developed. The predictive performance of the nomogram was evaluated in both the training and validation cohorts.

No statistically significant difference in clinical and pathologic characteristics were observed between the training and validation cohorts. In training cohort, significant differences were identified between the recurrence and non-recurrence groups in tumor size, nodule-in-nodule architecture, mosaic architecture, non-smooth tumor margin, intratumor necrosis, satellite nodule, and peritumoral hypo-intensity in the hepatobiliary phase (HBP). The results of multivariate analysis identified tumor size (HR, 1.435; 95 % CI, 0.702-2.026; p < 0.05), mosaic architecture (HR, 0.790; 95 % CI, 0.421-1.480; p < 0.05), non-smooth tumor margin (HR, 1.775; 95 % CI, 0.941-3.273; p < 0.05), intratumor necrosis (HR, 1.414; 95 % CI, 0.807-2.476; p < 0.05), satellite nodule (HR, 0.648; 95 % CI, 0.352-1.191; p < 0.01), peritumoral hypo-intensity on HBP (HR, 2.786; 95 % CI, 1.141-6.802; p < 0.001) and D (HR, 0.658; 95 % CI,0.487-0.889; p < 0.01) were the independent risk factor for recurrence. The nomogram exhibited excellent predictive performance with C-index of 0.913 and 0.875 in the training cohort and validation cohort, respectively. Also, based on the nomogram score, the patients were classified according to risk factor and the Kaplan-Meier curve analysis also showed that the nomogram had a good predictive efficacy.

The nomogram, integrating radiological risk factors and diffusion parameters, offers a reliable tool for preoperative prediction of early recurrence in HCC patients.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with conventional treatments often accompanied by severe side effects. Recently, nanozymes have been extensively employed in cancer therapy due to their enhanced enzymatic activities, stability compared to native enzymes. However, a standalone nanozyme exhibits insufficient targeting capability and fails to specifically localize to the pathological site. In this study, we successfully synthesized a multifunctional iron-based-nanozyme delivery system - Fe3O4-OA-DHCA-PEI-MAN@DSF modified with PEI and MAN by the thermal decomposition method. This mannose-modified nanozyme can specifically target HCC cells via an external magnetic field and mannose-mannose receptor (MRC2) binding. In addition, it exhibits good biocompatibility and pH-dependent drug release characteristics. Within the acidic tumor microenvironment, the iron-based nanozyme initiates intracellular fenton reactions, boosting reactive oxygen species (ROS) production, which ultimately induces apoptosis in HCC cells. Concurrently, the disulfiram small molecule released from the Fe3O4-OA-DHCA-PEI-MAN@DSF nanozyme binds to the FROUNT factor within monocyte-macrophages, thereby inhibiting their response to chemotactic signals emitted by liver cancer cells. This process ultimately suppresses the recruitment of macrophages by HCC cells, reshaping the tumor microenvironment and supporting effective liver cancer treatment. Moreover, this nanozyme system holds potential for MRI-guided targeted chemotherapy combined with chemodynamic therapy, aiming to refine the early diagnosis and precision treatment of hepatic carcinoma, and paving the way for the creation of sophisticated integrated nanoplatforms melding diagnostic and therapeutic functionalities.

Lidocaine, the most widely used local anaesthetic, has anticancer effects in both laboratory findings and retrospective clinical studies. We explored the potential benefits of intra-arterial lidocaine on long-term survival in patients with hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolisation (TACE).

This retrospective cohort study included patients with HCC who received TACE as initial treatment from August 2011 to October 2016. Eligible patients were categorised into no lidocaine and lidocaine groups. Propensity score matching was undertaken. Progression-free survival (PFS) and overall survival were compared between the two groups. Subgroup analysis was performed to explore the survival benefit of combining intra-arterial lidocaine with platinum-based chemotherapy during TACE.

Of 374 eligible patients, 96 were in the lidocaine group and 278 were in the no lidocaine group. Survival analysis showed that intra-arterial lidocaine was associated with longer PFS (P=0.004) and overall survival (P<0.001). After propensity score matching, PFS (P<0.001) and overall survival (P=0.001) benefits of lidocaine remained. Multivariate analysis showed that intra-arterial lidocaine was an independent prognostic factor for PFS (P=0.011) and overall survival (P=0.044). The impact of intra-arterial lidocaine was similar in patients receiving the TACE regimen with platinum (PFS: P=0.014; overall survival: P=0.023).

Intra-arterial lidocaine might improve long-term survival in patients with HCC undergoing TACE and in the subgroup of patients receiving platinum. The study highlights the potential antitumour benefits of combining lidocaine and chemotherapeutics in patients with cancer.

Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis B (CHB), with macrophage M2 polarization playing a critical role in shaping the tumor-promoting hepatic immune microenvironment. Sirtuin 1 (SIRT1) has been implicated in immune modulation and liver carcinogenesis. This study investigates the potential of Mimetic Nanoparticles (MNPs) for delivering SIRT1 inhibitors to regulate macrophage polarization and remodel the hepatic immune microenvironment, aiming to prevent HCC development post-CHB. A transgenic mouse model of CHB was established, and RNA sequencing (RNA-seq) and proteomics analyses revealed significant dysregulation of genes associated with M2 macrophage polarization, particularly SIRT1. Functional enrichment analysis highlighted key pathways, including PI3K-Akt and NF-κB, that contribute to CHB-driven immune alterations. Synthesized and characterized MNPs successfully delivered SIRT1 inhibitors, effectively inhibiting M2 macrophage polarization in vitro. In vivo administration of MNPs-SIRT1-FN significantly reduced M2 macrophage infiltration and suppressed tumor growth. These findings suggest that nanoparticle-mediated SIRT1 inhibition is a promising strategy for immunomodulation and HCC prevention in CHB patients. This study provides novel insights into nanoparticle-based immunotherapy for CHB-related HCC and highlights a potential therapeutic avenue for liver cancer prevention.

This study aimed to explore the role of the VEGFa/VEGFR2 autocrine pathway in cinobufagin-induced inhibition of hepatocellular carcinoma metastasis.

A CCK-8 assay was performed to assess cell viability. Scratch healing, Transwell, and sphere formation assays were used to measure the effects of cinobufagin on cell migration, invasion, and tumor sphere formation. An immunofluorescence double staining method was used to detect the localization of VEGFa and VEGFR2. The effects of inhibiting the VEGFa/VEGFR2 autocrine pathway on Huh7 cell metastasis and the effects of the VEGFa/VEGFR2 autocrine pathway on the regulation of PI3K/AKT-dependent migration, invasion, and epithelial‒mesenchymal transition were examined through use of the VEGFR2 inhibitor apatinib and the PI3K inhibitor LY294002. The effects of cinobufagin on the VEGFa/VEGFR2 autocrine pathway and tumor metastasis were assessed in transplanted tumors.

Cinobufagin inhibited Huh7 cell viability, migration, invasion, and tumor sphere formation in a dose-dependent manner. In addition, colocalization between VEGFa and VEGFR2 was detected in Huh7 cells. The results revealed that apatinib treatment significantly inhibited PI3K/AKT-dependent migration, invasion, and epithelial‒mesenchymal transition. The VEGFa/VEGFR2 autocrine pathway, the PI3K/AKT pathway, and epithelial-mesenchymal transition-associated protein markers were attenuated by cinobufagin in Huh7 cells. Additionally, cinobufagin attenuated the growth of hepatocellular carcinoma tumors in the Huh7 xenograft model and significantly downregulated the VEGFa/VEGFR2 autocrine pathway, the PI3K/AKT pathway, and the epithelial‒mesenchymal transition.

Cinobufagin may attenuate the PI3K/AKT-dependent metastatic potential of hepatocellular carcinoma by inhibiting the VEGFa/VEGFR2 autocrine pathway.

Metabolic reprogramming plays an important role in therapeutic efficacy of hepatocellular carcinoma (HCC). However, the metabolic reprogramming-related key genes associated with transcatheter arterial chemoembolization (TACE) treatment sensitivity in HCC remain further investigation.

We analyzed data from public databases, The Cancer Genome Atlas and Gene Expression Omnibus, as well as metabolism-related genes (MRGs), to identify key genes associated with TACE treatment sensitivity. Further analysis was conducted on the relationship between key genes and immune cell infiltration, HCC-related genes, regulatory network construction, nomogram construction, and drug sensitivity analysis. Finally, the expression of key genes was validated based on databases and in vitro RT-qPCR.

Four key genes (CDC20, LPCAT1, PON1, and SPP1) associated with TACE treatment sensitivity were identified. Increased CDC20, LPCAT1, and SPP1 and reduced PON1 were found in tumor tissues than normal tissues, as well as in advanced patients than early-stage patients. Lower expression of CDC20, LPCAT1, and SPP1, and higher expression of PON1 were detected in responsive patients than non-responsive patients. Patients with high expression of CDC20, LPCAT1, and SPP1, and low expression of PON1 had poor prognosis. They were also correlated with tumor immune microenvironment and sensitivity to multiple chemotherapy drugs. The expressions of key genes at the gene and protein levels were validated.

Our study provided systematic insights into identification of biomarkers for TACE treatment sensitivity in HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by aggressive progression and poor prognosis. Pathological angiogenesis in HCC is closely linked to metabolic reprogramming, particularly concerning fatty acid metabolism. The interplay between fatty acid metabolism and ferroptosis, a type of cell death driven by lipid peroxidation, is emerging as a crucial area of study. The transcription factor SOX4 is known to be overexpressed in various cancers, including HCC, and may play a key role in these processes. We assessed SOX4 expression in HCC using clinical samples and data from online databases. Next-generation RNA sequencing was employed to explore the effects of SOX4 on fatty acid metabolism, focusing on the CHREBP pathway. Functional assays, including lipid peroxidation and angiogenesis studies, were conducted to investigate the role of SOX4 in regulating ferroptosis and angiogenesis in HCC. SOX4 was found to be significantly upregulated in HCC and associated with enhanced angiogenesis. Mechanistically, SOX4 activated the CHREBP/SCD1 pathway, leading to increased production of monounsaturated fatty acids, which in turn inhibited ferroptosis. This suppression of ferroptosis contributed to the promotion of angiogenesis and tumor progression in HCC. In conclusion, SOX4 reprograms fatty acid metabolism via the CHREBP/SCD1 pathway, thereby inhibiting ferroptosis and promoting angiogenesis in HCC. These findings suggest that targeting the SOX4-CHREBP axis could represent a novel therapeutic strategy for HCC.

Objective: The primary objective of this study was to develop and validate a predictive nomogram that integrates radiomic features derived from contrast-enhanced computed tomography (CECT) images with clinical variables to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) after surgical resection. Methods: This retrospective study analyzed the preoperative enhanced CT images and clinical data of 202 patients with HCC who underwent surgical resection at the Affiliated Hospital of North Sichuan Medical College (Institution 1) from June 2017 to June 2021 and at Nanchong Central Hospital (Institution 2) from June 2020 to June 2022. Among these patients, 162 patients from Institution 1 were randomly divided into a training cohort (112 patients) and an internal validation cohort (50 patients) at a 7:3 ratio, whereas 40 patients from Institution 2 were assigned as an independent external validation cohort. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify clinical risk factors associated with OS after HCC resection. Using 3D-Slicer software, tumor lesions were manually delineated slice by slice on preoperative non-contrast-enhanced (NCE) CT, arterial phase (AP), and portal venous phase (PVP) images to generate volumetric regions of interest (VOIs). Radiomic features were subsequently extracted from these VOIs. LASSO Cox regression analysis was employed for dimensionality reduction and feature selection, culminating in the construction of a radiomic signature (Radscore). Cox proportional hazards regression models, including a clinical model, a radiomic model, and a radiomic-clinical model, were subsequently developed for OS prediction. The predictive performance of these models was assessed via the concordance index (C-index) and time-ROC curves. The optimal performance model was further visualized as a nomogram, and its predictive accuracy was evaluated via calibration curves and decision curve analysis (DCA). Finally, the risk factors in the optimal performance model were interpreted via Shapley additive explanations (SHAP). Results: Univariate and multivariate Cox regression analyses revealed that BCLC stage, the albumin-bilirubin index (ALBI), and the NLR-PLR score were independent predictors of OS after HCC resection. Among these three models, the radiomic-clinical model exhibited the highest predictive performance, with C-indices of 0.789, 0.726, and 0.764 in the training, internal and external validation cohorts, respectively. Furthermore, the time-ROC curves for the radiomic-clinical model showed 1-year and 3-year AUCs of 0.837 and 0.845 in the training cohort, 0.801 and 0.880 in the internal validation cohort, and 0.773 and 0.840 in the external validation cohort. Calibration curves and DCA demonstrated the model's excellent calibration and clinical applicability. Conclusions: The nomogram combining CECT radiomic features and clinical variables provides an accurate prediction of OS after HCC resection. This model is beneficial for clinicians in developing individualized treatment strategies for patients with HCC.

Primary liver cancer ranks as the sixth most prevalent malignant tumor and stands as the second leading cause of cancer-related mortality globally, posing a significant threat to public health. Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Surgical resection remains the cornerstone treatment for achieving radical cure and prolonged survival in HCC patients. Contrary to Western countries, the majority of HCC patients in China present with hepatitis B virus infection and consequent liver cirrhosis, with most cases diagnosed at an intermediate or advanced stage. This complexity results in a poor prognosis. Recent advancements in local therapeutic techniques and the introduction of systemic therapies, including targeted and immunotherapy agents, have provided new avenues for both clinical and basic conversion therapy for advanced HCC. Integrating multi-dimensional local and systemic therapies, multi-modal sequential, and comprehensive multidisciplinary approaches into the management of HCC patients has demonstrated promising conversion success rates. This holistic management strategy involves combining multiple treatment modalities vertically and coordinating various disciplines horizontally. However, significant challenges remain, including the precise selection of patients eligible for conversion therapy, the optimal choice of conversion therapy regimens, and the accurate determination of surgical timing post-conversion therapy. Addressing these challenges is crucial for hepatobiliary surgeons. High-quality, randomized controlled trials are urgently needed to generate robust evidence for clinical practice. This review aims to synthesize the latest research developments both in China and internationally and examines key issues in the realm of HCC conversion therapy.

Hepatocellular carcinoma (HCC) is a common malignancy associated with high morbidity and mortality rates worldwide. To improve the prognosis of HCC, early diagnosis is crucial. However, to date, little is known about the role of natural killer cell-related genes (NKCRGs) in predicting the prognosis of hepatocellular carcinoma patients. In this study, we identified 24 differentially expressed NKCRGs in HCC specimens from the TCGA dataset, including 22 upregulated genes and 2 downregulated genes. Functional enrichment analysis revealed that these genes were mainly involved in immune response pathways and various cancer-related pathways. Univariate analysis identified 21 prognostic NKCRGs, with eight genes (PAK1, MAP2K2, MAPK3, PLCG1, SHC1, HRAS, NRAS, and MICB) confirmed to be involved in HCC prognosis through Venn diagram analysis. A prognostic model was developed using LASSO-Cox regression, incorporating four genes (MAP2K2, SHC1, HRAS, and NRAS). The model's risk score was significantly associated with overall survival (OS) in both the TCGA and ICGC cohorts. Patients with high-risk scores had poorer OS, as demonstrated by Kaplan-Meier curves and ROC analyses. The risk score was not significantly correlated with gender or age but was higher in patients with advanced tumor grades and stages. Immune status analysis using ssGSEA showed higher enrichment scores for various immune cells and pathways in the high-risk group. Additionally, the risk score was positively correlated with the immune score, indicating its potential role in tumor microenvironment modulation. Expression analysis revealed that HRAS, SHC1, MAP2K2, and NRAS were upregulated in HCC tissues, with higher expressions of HRAS, MAP2K2, and NRAS associated with shorter OS. Knockdown experiments confirmed that silencing NRAS suppressed the proliferation of HCC cells, highlighting its potential as a therapeutic target. Overall, our findings suggest that the identified NKCRGs, particularly NRAS, play crucial roles in HCC progression and could serve as valuable prognostic markers and therapeutic targets.

Hepatocellular carcinoma (HCC) is a common malignant tumor globally and in China, and its incidence and mortality rate are increasing year by year, and it faces many challenges and difficulties in treatment. Tyrosine kinase inhibitors (TKIs) have important roles in cell growth, proliferation, and differentiation, and have now become important drugs for cancer treatment. There are no bibliometric studies on liver cancer and TKIs to date.

We retrieved 2848 records from the Web of Science™ Core Collection (WoSCC) database and analyzed them scientifically and metrically using CiteSpace and VOSviewer in terms of temporal and spatial distributions, author distributions, journal distributions, references, and keywords.

From January 1, 2004, to December 31, 2023, the WoSCC database documented 2848 publications related to tyrosinase inhibitors in HCC, comprising 2151 articles and 697 reviews. This literature involved 80 countries and regions, 3265 institutions, and 16,653 authors. Analysis shows a steady increase in publications annually since 2004, divided into 3 phases: 2004 to 2010 with fewer than 100 papers annually, suggesting minimal research attention; 2011 to 2019 with gradual growth, indicating increasing research interest; and a rapid surge post-2020, peaking in 2023, signaling heightened global interest in this field.

Our bibliometric analysis on TKIs and HCC spans years, countries, institutions, authors, disciplines, and journals. Since 2004, this field has gained attention, with current research focusing on inflammatory and immune mechanisms, associated diseases, cytokines, and TKIs' applications in liver cancer treatment, including combination therapies. These areas signify emerging research directions.

Extensive exploratory studies have been conducted and promising progress has been made in the use of nanomaterials for the diagnosis and treatment of hepatocellular carcinoma (HCC). Here, we aimed to reveal the evolution and trends in this field through bibliometric analysis.

English-language publications (1999-2024) in the field of nanomaterials and HCC were retrieved from the Web of Science database, and eligible articles were selected for bibliometric analysis (data extraction, statistical analysis, and visualization) using VOSviewer and Citespace software.

A total of 1617 eligible publications were analyzed. The number of publications increased rapidly from 2012 and peaked in 2020. China contributed the most publications, and the United States had the most citations. The Chinese Academy of Sciences was the most influential institution. The "International Journal of Nanomedicine (DOVE Medical)" published the most articles, while "Biomaterials (Elsevier)" was the most influential journal. Jie Tian had the highest number of publications, and Dan Shao had the highest average citation per article. Keyword analysis revealed that nanoparticles for targeted drug delivery, therapy and imaging of HCC were research hotspots. Keywords with citation bursts in the last three years included photodynamic therapy, sorafenib, and tumor microenvironment. Nano-vaccines, nano-antibodies, and synergistic therapies were emerging therapeutic strategies. A total of seven clinical trials were published, but to date there have been no major breakthroughs in HCC therapy using nanomaterials.

Research on nanomaterials and HCC has shown an overall upward trend, with research hotspots and frontiers focusing on nanoparticle-targeted chemotherapies, photodynamic therapy, and related tumor microenvironment research.

Liver cancer is challenging to detect in its early stages, and the global incidence rate and mortality associated with this disease have reached alarming levels. Currently, treatment options for liver cancer are limited, and there is a significant lack of safe and effective therapeutic agents. Esculetin is a natural product, exhibits almost non-toxic and inhibitory properties against various malignancies, making it a subject worthy of further investigation in liver cancer.

In this study, potential targets of esculetin in liver cancer were identified through transcriptomics, network pharmacology, and molecular docking technologies, and gene interference. Direct binding targets of esculetin were identified using surface plasmon resonance (SPR). The molecular mechanisms by which esculetin affects glucose metabolism in liver cancer were also explored. Finally, the activity against liver cancer and mechanisms of action of esculetin were validated in vivo using a mouse tumor model.

Glucose-6-phosphate isomerase (GPI) was shown to have a direct binding affinity for this compound. Esculetin inhibits glycolysis in liver cancer through its interaction with GPI and it was shown to exert a significant inhibitory effect on the genes and proteins associated with glycolysis such as ALDOA, ENO1, GAPDH, LDHA, PFKL, PGAM1, PGK1, and PKM2. Furthermore, esculetin not only suppresses the growth of liver cancer cells in vitro but also exhibits notable anti-tumor effects in vivo.

This study demonstrated the inhibitory effects of esculetin against liver cancer both in vitro and in vivo, demonstrating inhibition of glycolysis in liver cancer cells. In addition, the key glycolysis enzyme GPI was identified as a direct target of esculetin.

Manipulating biology through chemistry is older than the discipline of chemistry itself. Traditionally, selectivity of oral or intravenous drugs relied on preferential drug-receptor binding. A novel approach exploiting image-guided techniques to impart spatial selectivity opens up a wide range of new possibilities for study and manipulation of biology. Motivated initially by the poor prognosis for solid tumors such as liver cancer, we demonstrate the use of an extreme form of in vivo chemistry for targeted delivery of 2-propylpentanoyl chloride in a swine model. The ensuing reaction in tissue devitalizes it by multiple mechanisms with lasting effects and, critically, demonstrates very low systemic exposure compared to controls. This work points toward a new, powerful strategy for investigating the interface between chemistry and biology in vivo.

The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus (EBV), the first virus confirmed to cause human cancer. Viral infections significantly contribute to the global cancer burden, with seven known Group 1 oncogenic viruses, including hepatitis B virus (HBV), human papillomavirus (HPV), EBV, Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), and human immunodeficiency virus (HIV). These oncogenic viruses induce cellular transformation and cancer development by altering various biological processes within host cells, particularly under immunosuppression or co-carcinogenic exposures. These viruses are primarily associated with hepatocellular carcinoma, gastric cancer, cervical cancer, nasopharyngeal carcinoma, Kaposi sarcoma, lymphoma, and adult T-cell leukemia/lymphoma. Understanding the mechanisms of viral oncogenesis is crucial for identifying and characterizing the early biological processes of virus-related cancers, providing new targets and strategies for treatment or prevention. This review first outlines the global epidemiology of virus-related tumors, milestone events in research, and the process by which oncogenic viruses infect target cells. It then focuses on the molecular mechanisms by which these viruses induce tumors directly or indirectly, including the regulation of oncogenes or tumor suppressor genes, induction of genomic instability, disruption of regular life cycle of cells, immune suppression, chronic inflammation, and inducing angiogenesis. Finally, current therapeutic strategies for virus-related tumors and recent advances in preclinical and clinical research are discussed.

Advanced hepatocellular carcinoma (HCC) is characterized by poor prognosis, primarily due to limited therapeutic options and resistance to treatment. Although the combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has shown promising potential, the underlying mechanisms remain inadequately understood. Here, serine/threonine-specific protein phosphatase (PP1A) is upregulated in Lenvatinib-resistant HCC cells and correlates with poor prognosis. Functional experiments revealed that PP1A promotes HCC progression both in vitro and in vivo. Transcriptomic analysis and ferroptosis metabolite profiling (e.g., ROS, Fe2⁺, lipid-ROS, and GSH) demonstrated that PP1A inhibits Lenvatinib-induced ferroptosis by dephosphorylating Keap1 at site 104. This disruption of the Keap1-Nrf2 interaction enhances the transcription of ferroptosis-related markers and immune checkpoint PD-L1. Notably, single-cell sequencing and co-culture experiments revealed that PP1A knockdown alleviates T cell exhaustion and immune evasion, thereby improving antitumor immunity. In vivo experiments further demonstrated that PP1A knockdown significantly enhances the efficacy of Lenvatinib-ICIs combination therapy. Overall, our findings highlight PP1A as a critical regulator of ferroptosis and antitumor immunity, suggesting its potential as a predictive biomarker and therapeutic target for improving outcomes in advanced HCC.

Sappanone A (SA), a kind of homoisoflavanone extracted from the dry heartwood of Caesalpinia sappan L., has been shown to possess diverse bioactivities involving anti-inflammatory, antioxidant, and anti-apoptotic properties. Sustained proinflammatory state is a major factor in the occurrence and development of various diseases. Given the characteristics of SA, many studies have explored the effect of SA on inflammation-related diseases, which uncovered the multifaceted therapeutic potential of SA in such diseases. In this mini-review, we summarized the current achievements of SA on inflammation-related diseases (such as myocardial ischemia-reperfusion injury, liver injury, respiratory diseases, and kidney injury, etc.), in order to provide useful insights into the role of SA in inflammation-related diseases and benefit future clinical applications.

In hepatitis C patients with sustained virologic response (SVR) achieved after direct-acting antivirals (DAAs), the incidence of adverse clinical outcomes can be reduced but not completely eliminated. This meta-analysis aims at estimating the incidence of clinical outcomes in hepatitis C patients after achieving SVR with DAAs.

Literature search was carried out in PubMed, Cochrane Library database, Web of Science, and Embase. The primary endpoint was the incidence of hepatocellular carcinoma (HCC) occurrence, HCC recurrence, decompensated cirrhosis, and liver-related mortality, following DAA-induced elimination of hepatitis C virus (HCV). Subgroup analyses were performed according to age, gender, comorbidities, region, fibrosis stage, presence of decompensation, duration of follow-up, start point of follow-up, and HCC treatment modality. Furthermore, meta-regression was performed to explore sources of high heterogeneity.

Finally, 132 articles were included in our study. The pooled HCC occurrence rate was 1.50/100 person-years (95% CI, 1.35-1.65), HCC recurrence rate was 17.00/100 person-years (95% CI, 13.83-20.42), decompensation rate was 0.30/100 person-years (95% CI, 0.16-0.48), and liver-related mortality was 0.32/100 person-years (95% CI, 0.14-0.56). Meta-regression showed that duration of follow-up and fibrosis grade were important contributors to HCC occurrence. Age, start point of follow-up, and duration of follow-up were important contributors to HCC recurrence rate.

Patients with DAA-induced HCV elimination remain at risk for adverse outcomes, particularly those with cirrhosis and HCC history. The exposure to adverse outcomes tended to decrease over time, and the frequency and intensity of follow-up might be reduced in the future, which will require new scoring models to identify these individuals.

Hepatobiliary cancers are heterogeneous and molecularly complex. Recent advances in next-generation sequencing (NGS) have enhanced the understanding of their molecular landscape and enabled deployment of biomarker-based gene- and immune-targeted therapies. This review examines the role of molecular testing and targeted therapies in these malignant neoplasms.

Patients with hepatobiliary cancers have poor outcomes. Precision oncology studies have shown that while many common molecular alterations are not currently targetable in hepatocellular carcinoma (HCC), a large number of actionable alterations characterize biliary tract cancers (BTCs), with several therapies now approved by the US Food and Drug Administration. Immunotherapy is increasingly adopted in clinical practice, either as monotherapy or combined with cytotoxic chemotherapy, for both HCC and BTCs. Moreover, multiple solid cancer tumor-agnostic therapies are approved (larotrectinib, entrectinib, and repotrectinib for NTRK fusions; selpercatinib for RET fusions; dabrafenib and trametinib combination for BRAF V600E mutations; dostarlimab or pembrolizumab for tumors with high microsatellite instability and pembrolizumab for tumor mutation burden ≥10 mutations/megabase), highlighting the need for NGS as well as ERBB2 (formerly HER2) immunohistochemistry (IHC) (with the recent approval of solid tissue-agnostic deruxtecan trastuzumab for ERBB2-positive [IHC 3+] cancer) across cancers. N-of-1 clinical trials using customized drug combinations matched to the tumor's molecular profile have yielded encouraging results and provide a promising framework for future clinical trial design.

Molecular testing and gene- and immune-targeted therapies are transforming hepatobiliary cancer treatment. Tumor-agnostic and N-of-1 clinical trials have challenged traditional clinical trial paradigms and provide the foundation for truly personalized oncology for patients with these aggressive cancers. Further work is needed to determine how to leverage these novel approaches into the management of operable disease.

The majority of patients with hepatocellular carcinoma (HCC) miss the opportunity of radical resection, making immune check-point inhibitors (ICIs)-based conversion therapy a primary option. However, challenges persist in predicting response and identifying the optimal patient subset. The objective is to develop a CT-based clinical-radiomics model to predict durable clinical benefit (DCB) of ICIs-based treatment in potentially convertible HCC patients.

The radiomics features were extracted by pyradiomics in training set, and machine learning models was generated based on the selected radiomics features. Deep learning models were created using two different protocols. Integrated models were constructed by incorporating radiomics scores, deep learning scores, and clinical variables selected through multivariate analysis. Furthermore, we analyzed the relationship between integrated model scores and clinical outcomes related to conversion therapy in the entire cohort. Finally, radiogenomic analysis was conducted on bulk RNA and DNA sequencing data.

The top-performing integrated model demonstrated excellent predictive accuracy with an area under the curve (AUC) of 0.96 (95% CI: 0.94-0.99) in the training set and 0.88 (95% CI: 0.77-0.99) in the test set, effectively stratifying survival risk across the entire cohort and revealing significant disparity in overall survival (OS), as evidenced by Kaplan-Meier survival curves ( P < 0.0001). Moreover, integrated model scores exhibited associations with sequential resection among patients who achieved DCB and pathological complete response (pCR) among those who underwent sequential resection procedures. Notably, higher radiomics model was correlated with MHC I expression, angiogenesis-related processes, CD8 T cell-related gene sets, as well as a higher frequency of TP53 mutations along with increased levels of mutation burden and neoantigen.

The deep learning-based clinical-radiomics model exhibited satisfactory predictive capability in forecasting the DCB derived from ICIs-based conversion therapy in potentially convertible HCC, and was associated with a diverse range of immune-related mechanisms.

Ferroptosis can have a major impact on the development and advancement of hepatocellular carcinoma (HCC) due to its clear association with heightened vulnerability to the disease. This study aimed to develop a novel nanoplatform to evaluate its effectiveness in in vivo and in vitro models of HCC.

Erastin, a compound that induces iron-dependent cell death, and HMME, a sonosensitizer, were enclosed within mesoporous silica nanoparticles (MSNs). The nanoparticles were engineered to exhibit a responsive assembly-disassembly mechanism. Hydrophilic hyaluronic acid (HA) was utilized for conjugation modification to synthesize Erastin/HMME@MSNs-HA. In vivo and in vitro experiments were conducted to elucidate the antitumor mechanisms of this nanomaterial.

In the in vitro cellular experiments, Erastin/HMME@MSNs-HA was rapidly degraded by hyaluronidase, leading to increased endocytosis of the cancer cells. Cellular breakdown led to the generation of harmful reactive oxygen species (ROS), decreased glutathione levels, and increased lipid peroxidation, resulting in a decrease in mitochondrial membrane potential, dysfunctional mitochondria, reduced cell growth, and increased cell death. Additionally, the Erastin/HMME@MSNs-HA nanotherapy platform, when combined with ultrasound (US) treatment, exhibited significant therapeutic effectiveness against tumors in vivo. It induced significant cell death in cancerous tissues, decreased tumor growth, worsened tissue oxygen deprivation, and exhibited good compatibility with the body.

These findings indicate that the nanoplatform can effectively alleviate tumor hypoxia while inducing apoptosis and ferroptosis, laying the foundation for enhancing the efficacy of ROS-mediated HCC therapy.

Diffusion-weighted imaging and the quantified apparent diffusion coefficient (ADC) correlate with cell density and histopathological features in tumors. Radiomics analysis may provide more insight into the underlying microstructure and may better correlate with histopathology. The present study used cross-sectional guided biopsy specimens to exploit the precise spatial localization of the performed biopsy to correlate radiomics features of the ADC map with immunohistochemical features in hepatocellular carcinoma (HCC).

A total of 51 patients (11 female patients, 21.6 %) were included in the present study. The mean age was 71.9 ± 9.9 years, ranging from 42 to 91 years. Prebioptic liver MRI with diffusion-weighted imaging was used to correlate the radiomics features of the ADC maps with the immunohistochemical features quantified in liver biopsy. Proliferation potential Ki 67, leukocyte count and tumor-stroma ratio were evaluated as histopathological parameters.

The following ADC texture features were correlated with the Ki 67 index _MinNorm (r = -0.307, p = 0.03), Vertl_RLNonUni (r = - 0.309, p = 0.03), 135dr_RLNonUni (r = -0.346, p = 0.01). The texture feature _MinNorm achieved the best diagnostic accuracy with an area under the curve of 0.76 (95 % CI 0.60-0.91, p < 0.01) to discriminate between low and high proliferative HCC. Multiple statistically significant correlations were found between ADC texture features and tumor-stroma-ratio, the highest for S(0,1)Contrast (r = 0.460, p = 0.001). No statistically significant correlations were found between the ADC texture features with the CD45+ leukocyte count and grading.

Radiomics features of the ADC maps can reflect the underlying histopathology in HCC patients including the proliferation potential and tumor-stroma ratio but not CD45 positive cells and tumor grading. The complex interactions between quantitative imaging and histopathology need to be further investigated in a validation cohort.

Hepatocellular carcinoma (HCC) continues to pose a substantial worldwide health concern, marked by elevated mortality rates and restricted therapeutic alternatives. Recent studies have highlighted the potential of natural compounds as therapeutic agents in cancer management. This review focuses on the diagnostic and prognostic potential of microRNAs (miRNAs) as biomarkers in HCC, alongside the therapeutic promise of natural products. We explore the intricate role of miRNAs in the pathogenesis of HCC, detailing their regulatory functions in cellular processes such as proliferation, apoptosis, and metastasis. Additionally, we discuss the emerging evidence supporting the use of natural compounds, including phytochemicals, in modulating miRNA expression and their potential synergistic effects with conventional therapies. Key miRNAs discussed include miR-21, an oncogenic factor that promotes tumor growth by targeting the tumor suppressor phosphatase and tensin homolog (PTEN); miR-34a, which enhances apoptosis and may improve treatment efficacy when combined with c-MET inhibitors; miR-203, whose downregulation correlates with poor outcomes and may serve as a prognostic marker; miR-16, which acts as a tumor suppressor and has diagnostic potential when measured alongside traditional markers like alpha-fetoprotein (AFP); and miR-483-3p, associated with resistance to apoptosis and tumor progression. By integrating insights from recent studies, this review aims to highlight the dual role of miRNAs as both biomarkers and therapeutic targets, paving the way for enhanced diagnostic strategies and novel treatment modalities in HCC management.

In the clinic, Lipiodol chemotherapeutic emulsions remain a main choice for patients diagnosed with hepatocellular carcinoma (HCC) via the mini-invasive transarterial chemoembolization (TACE) therapy. However, the poor stability of conventional Lipiodol chemotherapeutic emulsions would result in the fast drug diffusion and incomplete embolization, inducing systemic toxicity and impairing the efficacy of TACE therapy. Therefore, it is of great importance to construct alternative formulations based on commercial Lipiodol to achieve the improved efficacy and safety of HCC treatment. Herein, calcium phosphate (CaP) nanoparticles-stabilized Lipiodol Pickering emulsion (CaP-LPE) with improved stability and pH-responsiveness is prepared and utilized for the encapsulation of combretastatin A4-phosphate (CA4P), a clinically approved vascular disrupting agent. The obtained CA4P-loaded CaP-LPE (CCaP-LPE) was shown to be enhanced stability compared to conventional Lipiodol emulsion and pH-responsive release of the encapsulated drugs. On one hand, the released CA4P could disrupt tumor vascular and cut off the blood supplying of tumor cells, thus starving cancer cells. Moreover, it was revealed that CCaP-LPE could reverse immunosuppressive tumor microenvironment (TME) by neutralizing tumor acidity, leading to the increased infiltration of CD8+ T cells and the decreased percentages of immunosuppressive cells. As the result, such CCaP-LPE could effectively shrink orthotopic N1S1 HCC tumors in rats by eliciting a potent antitumor immune response. Therefore, this study highlights a simple strategy to construct a novel LPE with the potencies of tumor vascular disruption and TME modulation, holding a great promise for TAE therapy of HCC.

Icaritin (ICT) shows great potential in cancer therapy. To enhance the cancer-fighting properties of icaritin against hepatocellular carcinoma (HCC), we developed icaritin-loaded liposomes modified with hyaluronic acid (HA-Lip-ICT). We employed statistical design methods to analyze how various factors affected particle dimensions and drug encapsulation, creating an optimized HA-Lip-ICT formulation that could effectively suppress HCC cell growth and trigger cellular aging. The human HCC cell line Huh7 was then exposed to different icaritin preparations. We assessed tumor cell viability through multiple assays, including colony formation and DNA synthesis measurements. Our results demonstrated that the refined HA-Lip-ICT significantly impaired HCC cell proliferation. Moreover, at a concentration of 10 μmol/L, HA-Lip-ICT markedly accelerated cellular senescence in HCC cells. These observations support our initial hypothesis that HA-Lip-ICT can inhibit HCC cell growth and promote their aging. While further research is needed to elucidate the exact mechanisms, this approach shows the promise of HA-Lip-ICT as a targeted therapy for improving the HCC treatments.

We sought to develop a predictive model to preoperatively identify patients with hepatocellular carcinoma (HCC) at risk of undergoing futile upfront liver resection (LR).

Patients undergoing curative-intent LR for HCC were identified from a large multi-institutional database. Futile LR was defined by death or disease recurrence within six months postoperatively. Backward logistic regression was performed to identify factors associated with futility. Additionally, binary criteria were established for surgical candidacy, aiming to keep the likelihood of futility below 20 %.

Among 1633 patients with HCC, 264 (16.2 %) underwent futile upfront LR. Tumor burden score (TBS) (coefficient: 0.083, 95%CI: 0.067-0.099), alpha-fetoprotein (AFP) (coefficient: 0.254, 95%CI: 0.195-0.310), and albumin-bilirubin (ALBI) grade 2/3 (coefficient: 0.566, 95%CI: 0.420-0.718) were independently associated with an increased risk of futile LR. The model demonstrated strong discrimination and calibration in both derivation and validation cohorts. Low, intermediate, and high-risk groups were determined based on the risk model, each with an escalating likelihood of futility, worse histological features, and worse survival outcomes. Six distinct conditions based on AFP-adjusted-to-TBS criteria were established, all with a futility likelihood of less than 20 %. Patients fulfilling these criteria had significantly better long-term recurrence-free and overall survival. The futility risk model was made available online for wide clinical applicability: (https://altaf-pawlik-hcc-futilityofsurgery-calculator.streamlit.app/).

A preoperative risk model and AFP-adjusted-to-TBS criteria were developed and validated to predict the likelihood of futile LR among patients with HCC. This pragmatic clinical tool may assist clinicians in preoperative decision-making, helping them avoid futile surgery unlikely to offer long-term benefits.

Morphologic criteria, such as the Barcelona Clinic Liver Cancer staging system often fail to accurately predict long-term survival among patients undergoing liver resection for hepatocellular carcinoma. We sought to develop a continuous risk score that incorporates established markers of tumor biology and liver function to improve the prediction of overall survival.

Data from a multi-institutional database were used to identify patients who underwent curative-intent hepatectomy for hepatocellular carcinoma. A predictive score for overall survival was developed using weighted beta-coefficients from a multivariable Cox regression model.

Among 850 patients, 595 (70.0%) were assigned to the training cohort, and 255 (30.0%) to the test cohort. In the training cohort, multivariable analysis identified the Model of End-Stage Liver Disease (hazard ratio, 1.04; 95% confidence interval, 1.01-1.07), log-transformed alpha-fetoprotein (hazard ratio, 1.07; 95% confidence interval, 1.02-1.13), and tumor burden score (hazard ratio, 1.07; 95% confidence interval, 1.03-1.11) as independent predictors of worse overall survival. The Model of End-Stage Liver Disease-alpha-fetoprotein-tumor burden score, based on the Cox model, stratified patients into low-risk (n = 466, 78.3%) with a 5-year OS of 70.5% and high-risk (n = 129, 21.7%) with a 5-year OS of 47.0% (P < .001). In the test cohort, the Model of End-Stage Liver Disease-alpha-fetoprotein-tumor burden score demonstrated superior discriminative accuracy (C-index: 0.72, time-dependent area under the curve 1-year: 0.80, 3-year 0.76, 5-year 0.70) compared with the Barcelona Clinic Liver Cancer staging system (C-index: 0.53, time-dependent area under the curve 1-year: 0.61, 3-year 0.55, 5-year 0.56). An online tool was made accessible at https://jk-osu.shinyapps.io/MELD_AFP_TBS/.

The Model of End-Stage Liver Disease-alpha-fetoprotein-tumor burden score provides a novel, accurate tool for prognostic stratification of patients with hepatocellular carcinoma, identifying high-risk patients who may benefit from alternative treatments to improve outcomes.

Liver cancer, notably hepatocellular carcinoma (HCC), poses a significant global health burden due to its high fatality rates. Conventional antitumor medications face challenges, including poor targeting, high toxicity, and drug resistance, leading to suboptimal clinical outcomes. This review focused on nanoparticle use in diagnosing and delivering medication for HCC, aiming to advance the development of nanomedicines for improved treatment outcomes. As an emerging frontier science and technology, nanotechnology has shown great potential, especially in precision medicine and personalized treatment. The success of nanosystems is attributable to their smaller size, biocompatibility, selective tumor accumulation, and lower toxicity. Nanoparticles, as a central part of nanotechnology innovation, have emerged in the field of medical diagnostics and therapeutics to overcome the various limitations of conventional chemotherapy, thus offering promising applications for improved selectivity, earlier and more precise diagnosis of cancers, personalized treatment, and overcoming drug resistance. Nanoparticles play a crucial role in drug delivery and imaging of HCC, with the body acting as a delivery system to target and deliver drugs or diagnostic reagents to specific organs or tissues, helping to accurately diagnose and target therapies while minimizing damage to healthy tissues. They protect drugs from early degradation and increase their biological half-life.

Polyamidoamine dendrimer (PAMAM) are effective carriers that transport diagnostic imaging reagents and drugs to the tumor site. Their excellent bio-compatibility and bio-degradability reduce damage to healthy tissues, resulting in improved treatment efficacy. Dendrimer molecules are particularly useful in targeted drug delivery within malignant cells. This article reviews recent progress of PAMAM in imaging and treating breast cancer, lung cancer, hepatocellular cancer, colorectal cancer, gastric cancer, prostate cancer, and glioblastoma. This review aims to provide new and feasible ideas for cancer diagnosis imaging and treatment while also serving as a significant reference point for personalized tumor therapy based on PAMAM materials.

Splicing factor 3b subunit 6(SF3B6), a subunit of the SF3B complex, regulates the process of RNA splicing by recognizing the branch point adenosine in pre-mRNA and facilitating the interaction between U2 snRNA and the branch point sequence. Currently, there is no systematic multi-omics study exploring the diagnostic, prognostic, and immunotherapy predictive value of SF3B6 in pan-cancer, nor is its role in hepatocellular carcinoma (HCC) clear.

We utilized various databases to systematically examine the expression and genetic variation of SF3B6 across multiple cancer types, assessing its relationship with diagnosis, prognosis, immune infiltration, immunotherapy response, and associated signaling pathways. Additionally, we investigated the correlation between SF3B6 and prognosis, clinicopathological features, and treatment responses in HCC, as well as the roles of its related alternative splicing isoforms. Finally, we conducted in vitro experiments to validate the effects of SF3B6 on the proliferation, migration, invasion, apoptosis, and cell cycle progression of liver cancer cells.

Results indicate that SF3B6 was highly expressed in various cancers and regulated by copy number variations and DNA methylation. The elevated expression of SF3B6 demonstrated predictive value for cancer diagnosis, prognosis, and responses to immunotherapy. Functional enrichment analysis suggests that SF3B6 was closely associated with pathways related to tumor immunity, tumor metabolism, and cell cycle. Additionally, high SF3B6 expression was an independent risk factor for overall survival and correlated with poor alpha-fetoprotein levels, pathological grading, clinical staging, and reduced responses to sorafenib and transarterial chemoembolization treatment in HCC. Interestingly, SF3B6 was associated with variant splicing isotypes of genes involved in the G2M checkpoint and DNA repair pathways, including NEIL3, NEK2, KIF4A, TROAP, and FANCD2. Moreover, SF3B6 was highly expressed in liver cancer cells, promoting the proliferation, migration, and invasion of cancer cells, inhibiting apoptosis, and regulating the transition from the S phase to the G2M phase of the cell cycle.

We emphasize that SF3B6 has the potential to serve as a biomarker for predicting cancer diagnosis, prognosis, and immunotherapy responses, especially in HCC. SF3B6 and its related alternative splicing isoforms promote the occurrence and progression of HCC and may serve as potential therapeutic targets.

Cirrhosis is closely related to hepatocellular carcinoma (HCC), however, the regulation of circular RNA (circRNA) in HCC with cirrhotic background has not yet been well illustrated. In this study, high throughput circRNA sequencing was applied to identified candidate circRNAs in HCC samples with cirrhotic background. The biological function of candidate circRNA was validated in both in vitro and in vivo settings. Additionally, Alphafold 3, mass spectrometry analysis and immunofluorescence were employed to investigate the underlying mechanisms involved. We found circCEP70 exhibited significantly higher expression levels in cirrhotic HCC samples and showed a positive correlation with improved prognosis. The RNA binding protein U2AF2 was found to suppress the expression of circCEP70 in cirrhosis patients. In vitro and in vivo experiments, including CCK-8, EdU, plate cloning, transwell, scratch, subcutaneous tumor formation, liver metastasis in situ, and lung metastasis assays confirmed the anti-carcinogenic effects. Mechanistically, circCEP70 encoded a novel protein named CEP70-160aa, which interacted with PKM2 and hindered its translocation into the nucleus. This interaction led to reduce STAT3 phosphorylation in the nucleus, thus inhibiting HCC proliferation and metastasis. In cirrhotic microenvironment, circCEP70 prevented HCC proliferation and metastasis through PKM2/STAT3 axis, and RNA binding protein U2AF2 could inhibit circCEP70 expression.

Minimally invasive needle-based interventions are commonly used in cancer diagnosis and treatment, including procedures, such as biopsy, brachytherapy, and microwave ablation. Although MR-guided needle placement offers several distinct advantages, such as high-resolution target visualization and accurate device tracking, one of the primary limitations that affect its widespread adoption is the ergonomic constraints of the closed-bore MRI environment, requiring the patients to be frequently moved in and out to perform the needle-based procedures. This paper introduces a low-profile, body-mounted, MR-guided robot designed to address this limitation by streamlining the operation workflow and enabling accurate needle placement within the MRI scanner.

The robot employs piezoelectric linear actuators and stacked Cartesian XY stages to precisely control the position and orientation of a needle guide. A kinematic model and control framework was developed to facilitate accurate targeting. Additionally, clinical workflow for the liver interventions was developed to demonstrate the robot's capability to replicate existing procedures. The proposed system was validated in benchtop environment and 3T MRI scanner to quantify the system performance.

Experimental validations conducted in free space demonstrated a position accuracy of 2.38 ± 0.94 mm and orientation error of 1.40 ± 2.89°. Additional tests to confirm MR-conditionality and MR-guided phantom placements were carried out to assess the system's performance and safety in MRI suite, yielding a position error of 2.01 ± 0.77 mm and an orientation error of 1.57 ± 1.31°.

The presented robot shows exceptional compatibility with a wide range of patients and bore sizes while maintaining clinically significant accuracy. Future work will focus on the validations in dynamic liver environments.