Hepatocellular Carcinoma Research Articles

Implementing palliative care in hepatocellular carcinoma ambulatory clinics-study protocol for Accelerated translational research in PRImary liver CAncer (APRICA) randomised controlled palliative care trial.

Integration of symptom and palliative care for people with advanced cancer is established in many tumour types, but its role in people with hepatocellular carcinoma (HCC) has not been clearly defined. This study aims to evaluate the clinical and cost effectiveness of an intervention involving a suite of strategies designed to assess and treat palliative care symptoms and needs in adult outpatients with HCC attending four New South Wales (NSW) metropolitan tertiary hospitals. This trial will use a pragmatic cluster-based randomised-controlled design, with ambulatory HCC services as the clusters. HCC patients will be recruited if they have Barcelona Clinical Liver Cancer (BCLC) stage A disease with active tumour or a current or prior diagnosis of BCLC stage B or C disease regardless of tumour activity. Patients with BCLC stage D disease will be excluded as palliative care is the standard of care (SOC) in this group. Cluster sites will be randomised to the study intervention or control where patients are managed according to SOC. All participants will complete the liver-specific Edmonton Symptom Assessment Scale (ESAS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at regular ambulatory clinic appointments. At intervention sites, patients scoring ≥ 5 on any liver-specific ESAS symptom will be referred to palliative care physicians for consultation. The primary clinical outcome will be improvement in all symptoms scored ≥ 5 on the liver-specific ESAS by 50% within 3months and the primary implementation outcome will recording the liver-specific ESAS in ≥ 80% of all participants attending clinic appointments. Caregivers of patients enrolled in the trial will be invited to perform Carer Support Needs Assessment Tool at each appointment. This trial will inform if earlier palliative care involvement significantly reduces the symptom burden associated with HCC. If found to be effective, earlier implementation of palliative care consultation should be included in HCC treatment guidelines. ACTRN12623000010695. Registered on September 1, 2023.

MicroRNA-206 as a promising epigenetic approach to modulate tumor-associated macrophages in hepatocellular carcinoma

This letter comments on the recently published manuscript by Huang et al in the World Journal of Gastroenterology , which focused on the immunomodulatory effect of Calculus bovis on hepatocellular carcinoma (HCC) tumor microenvironments (TME) by inhibiting M2-tumor-associated macrophage (M2-TAM) polarization via Wnt/β-catenin pathway modulation. Recent research highlights the crucial role of TAMs and their polarization towards the M2 phenotype in promoting HCC progression. Epigenetic regulation, particularly through microRNAs (miR), has emerged as a key factor in modulating immune responses and TAM polarization in the TME, influencing treatment responses and tumor progression. This editorial focuses on miR-206, which has been found to inhibit HCC cell proliferation and migration and promote apoptosis. Moreover, miR-206 enhances anti-tumor immune responses by promoting M1-polarization of Kupffer cells, facilitating CD8+ T cell recruitment and suppressing liver cancer stem cell expansion. However, challenges remain in understanding the precise mechanisms regulating miR-206 and its potential as a therapeutic agent. Targeting epigenetic mechanisms and improving strategies, whether through pharmacological or genetic approaches, offer promising avenues to sensitize tumor cells to chemotherapy. Understanding the intricate interactions between cancer and non-coding RNA regulation opens new avenues for developing targeted therapies, potentially improving HCC prognosis.

DKK1+ tumor cells inhibited the infiltration of CCL19+ fibroblasts and plasma cells contributing to worse immunotherapy response in hepatocellular carcinoma.

Intra-tumor immune infiltration plays a pivotal role in the interaction with tumor cells in hepatocellular carcinoma (HCC). However, its phenotype and related spatial structure remained elusive. To address these limitations, we conducted a comprehensive study combining spatial data (38,191 spots from eight samples) and single-cell data (56,022 cells from 20 samples). Our analysis revealed two distinct infiltration patterns: immune exclusion and immune activation. Plasma cells emerged as the primary cell type within intra-tumor immune clusters. Notably, we observed the co-location of CCL19+ fibroblasts with plasma cells, which secrete chemokines and promote T-cell activation and leukocyte migration. Conversely, in immune-exclusion samples, this co-location was primarily observed in the adjacent normal area. This co-localization correlated with T cell infiltration and the formation of tertiary lymphoid structures, validated by multiplex immunofluorescence conducted on twenty HCC samples. Both CCL19+ fibroblasts and plasma cells were associated with favorable survival outcomes. In an immunotherapy cohort, HCC patients who responded favorably exhibited higher infiltration of CCL19+ fibroblasts and plasma cells. Additionally, we observed the accumulation of DKK1+ tumor cells within the tumor area in immune-exclusion samples, particularly at the tumor boundary, which inhibited the infiltration of CCL19+ fibroblasts and plasma cells into the tumor area. Furthermore, in immune-exclusion samples, the SPP1 signaling pathway demonstrated the highest activity in communication between tumor and immune clusters, and CCL19-CCR7 played a pivotal role in the self-communication of immune clusters. This study elucidates immune exclusion and immune activation patterns in HCC and identifies relevant factors contributing to immune resistance.

MRI Tomoelastography to Assess the Combined Status of Vessels Encapsulating Tumor Clusters and Microvascular Invasion in Hepatocellular Carcinoma.

Integrating vessels encapsulating tumor clusters (VETC) and microvascular invasion (MVI) (VM hereafter) is potentially useful in risk stratification of hepatocellular carcinoma (HCC). However, noninvasive assessment methods for VM are lacking. To investigate the diagnostic performance of tomoelastography in assessing the VM status in HCC. Retrospective. One hundred sixty-eight patients with surgically confirmed HCC consisting of 115 training and 53 validation cohorts, divided into negative-VM and positive-VM groups with mild or severe-VMs. Of them, 127 patients completed the follow-up (median: 26.1 months). 3D multifrequency tomoelastography with a single-shot spin-echo echo-planar imaging sequence, and liver MRI including T1-weighted in-phase and opposed-phase gradient echo (GRE), T2-weighted turbo spin echo, diffusion-weighted imaging and dynamic contrast-enhanced T1-weighted GRE sequences at 3.0 T. Shear wave speed (c) and phase angle of the shear modulus (φ) were calculated on tomoelastograms. Imaging features were visually analyzed and clinical features were collected. Conventional models used clinical and imaging features while nomograms combined tomoelastography, clinical and imaging features. Univariable and multivariable logistic regression analyses, nomogram, area under the receiver operating characteristic curve (AUC), DeLong test, Kaplan-Meier analysis and log-rank test. P < 0.05 was considered statistically significant. Tumor-to-liver parenchyma ratio of c (cr) and tumor c were independent risk factors for positive-VM and severe-VM, respectively. In validation cohort, the nomograms including cr and tumor c performed significantly better than the conventional models for diagnosing positive-VM (0.84 [95% CI: 0.72-0.93] vs. 0.77 [95% CI: 0.64-0.88]) and severe-VM (0.86 [95% CI: 0.68-0.96] vs. 0.75 [95% CI: 0.55-0.89]). Patients with estimated positive-VM (9.3 months)/severe-VM (9.2 months) based on nomograms had shorter median recurrence-free survival than those with estimated negative-VM (>20.0 months)/mild-VM (18.0 months) in validation cohort. Tomoelastography based-nomograms showed good performance for noninvasively assessing VM status in patients with HCC. 3 TECHNICAL EFFICACY: Stage 2.

Genetic variants in folate metabolism-related genes, serum folate and hepatocellular carcinoma survival: the Guangdong Liver Cancer Cohort study.

Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNPin three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.

Harnessing the power of Calculus bovis: Anti-cancer properties and Wnt pathway modulation in hepatocellular carcinoma

In this manuscript, we comment on the article, which explores the anti-cancer effects of Calculus bovis (CB) in tumor biology. We highlight its potential, particularly in hepatocellular carcinoma (HCC), where it inhibits the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways and induces apoptosis. CB contains compounds such as oleanolic acid and ursolic acid that target interleukin-6, mitogen-activated protein kinase 8, vascular endothelial growth factor, and caspase-3, offering anti-inflammatory and hepatoprotective benefits. The manuscript also discusses CB sativus (CBS), an artificial substitute, which has shown efficacy in reducing hepatic inflammation and oxidative stress in animal models. We emphasize the need for further research on the effects of CBS on the gut-liver axis and gut microbiota, and on targeting Wnt signaling and M2 tumor-associated macrophage as potential therapeutic strategies against HCC.

Harnessing the power of Calculus bovis: Anti-cancer properties and Wnt pathway modulation in hepatocellular carcinoma

In this manuscript, we comment on the article, which explores the anti-cancer effects of Calculus bovis (CB) in tumor biology. We highlight its potential, particularly in hepatocellular carcinoma (HCC), where it inhibits the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways and induces apoptosis. CB contains compounds such as oleanolic acid and ursolic acid that target interleukin-6, mitogen-activated protein kinase 8, vascular endothelial growth factor, and caspase-3, offering anti-inflammatory and hepatoprotective benefits. The manuscript also discusses CB sativus (CBS), an artificial substitute, which has shown efficacy in reducing hepatic inflammation and oxidative stress in animal models. We emphasize the need for further research on the effects of CBS on the gut-liver axis and gut microbiota, and on targeting Wnt signaling and M2 tumor-associated macrophage as potential therapeutic strategies against HCC.

Non-liver malignancies as main cause of mortality after HCV eradication among people living with HIV

Background. In people living with HIV (PLWH) with HCV infection, liver and non-liver-related mortality significantly decreased after receiving direct acting antivirals (DAAs). We aimed to assess main causes and predictors of mortality after sustained virological response (SVR) induced by DAAs. Methods. Retrospective study in antiretroviral treatment-experienced PLWH with HCV infection, followed at San Raffaele Hospital, Milan, Italy, who achieved SVR after DAAs. Kaplan-Meier analysis and log-rank test were used to estimate cumulative probability of death for any cause. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) of death and the corresponding 95% confidence interval (95%CI); Baseline variables included in the model were: age, diabetes, hepatocellular carcinoma (HCC), α-fetoprotein (AFP), ALBI grade. Results. Among 663 people included with a median follow-up of 4.4 years (IQR=3.5-5.5), 49 died. Overall 5-year cumulative probability of death was 8.0% (95%CI=5.5%-10.4%); 63.2% (n=31/49) died from non-liver-related events [mainly non-liver malignancies (18/49) and cardiovascular events (7/49)].-. At multivariate analysis, death was more likely in older people [aHR (adjusted Hazard Ratio) (5-year older)=1.46, 95%CI=1.16-1.83, p=0.0009], and in people with diabetes [aHR=2.98, 95%CI=1.55-5.71, p=0.001], ALBI grade ≥2 [aHR=2.13, 95%CI=1.17-3.90, p=0.014] and AFP ≥3.4 ng/mL [aHR=1.96, 95%CI=1.01; 3.84, p=0.049]. Conclusions. In our cohort, non-liver-related events and malignancies were the most common cause of death after HCV eradication. Diabetes, ALBI grade ≥2 and AFP≥ 3.4 ng/L were associated with higher risk of death. In PLWH after HCV eradication, regardless of liver disease stage, surveillance of non-liver events, particularly malignancies, should be recommended.

Patient considerations when using ritlecitinib for alopecia areata in adolescents: Guidance for the clinicians

Background: Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss that can affect children, adolescents, and adults. Ritlecitinib, an orally administered Janus kinase (JAK) 3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family inhibitor, is the first and currently the only treatment approved by the United States Food and Drug Administration for adolescents (aged 12-17 years) with severe AA. Summary: The ALLEGRO Phase 2b–3 trial demonstrated that 25% and 50% of adolescents with a Severity of Alopecia Tool (SALT) score ≥50 at baseline achieved a SALT score ≤20 at week 24 and week 48 after receiving 50mg ritlecitinib daily, respectively. The most common adverse events were headache, acne, and nasopharyngitis in adolescents. This review summarizes the mechanism of action, clinical trial evidence on efficacy and safety profile, factors associated with treatment response to JAK inhibitors for AA, and vaccination considerations for adolescents. Key Messages: This review aims to facilitate the risk-benefit assessment and shared decision-making between clinicians and patients and provide clinical considerations and management recommendations for ritlecitinib use in adolescents with AA.

Smart Mesoporous Silica Nanoparticles Loading Curcumin Inhibit Liver Cancer.

Curcumin (CUR) as one of the natural edible pigments is approved by the World Health Organization due to its nontoxic and anticancer effect. However, the utility of CUR is restricted due to its low oral bioavailability. Nanoparticle drug delivery systems like mesoporous silica nanoparticles (MSNs) have been extensively used due to their high specific surface area, high loading rate, and ease of modification. This study developed lactobionic acid (LA)-modified carboxymethyl chitosan (CMCS)-coated MSNs to deliver CUR specifically targeting hepatocellular carcinoma. Among these nanoparticles, LA targets liver cancer cells. CMCS utilizes pH-responsive release of CUR. The LA-CMCS-MSN@CUR (MSN@CUR) were evaluated using several methods, including Fourier transform infrared spectroscopy, transmission electron microscopy, and zeta potential measurements. Liver cellular uptake of MSN@CUR depends on a specific LA receptor-mediated endocytosis mechanism. Additionally, MSN@CUR performed with a better antitumor effect than Cur in H22 orthotopic transplantation of liver cancer and H22 solid tumor mouse models. Treatment with MSN@CUR significantly reduced the protein of VEGF, p-PI3K, and AKT, increased the protein of caspases 3 and 8, ultimately inhibited tumor migration, and promoted apoptosis. This study provides a new path for delivery of natural active ingredients with excellent bioavailability in the antitumor field.

FKBP4 promotes glycolysis and hepatocellular carcinoma progression via p53/HK2 axis.

FKBP4, a member of the FK506-binding protein (FKBP) family, is a promising target for a variety of disorders, including cancer. However, its underlying molecular mechanism and potential function in hepatocellular carcinoma (HCC) are largely elusive. Therefore, we aimed to investigate the expression status, functional implications and underlying mechanisms of FKBP4 in HCC. Our bioinformatics analysis of TCGA LIHC datasets, ICGC LIRI-JP datasets and GEO datasets results showed FKBP4 was upregulated in HCC tissues. We also confirmed the elevated FKBP4 in clinical HCC samples. Additionally, quantitative RT-PCR results revealed FKBP4 was highly expressed in all five tested HCC cell lines. We also observed a correlation between elevated FKBP4 expression and poor prognosis in HCC patients. Loss of FKBP4 can inhibit the proliferation and migration in HCC cells. Furthermore, we found that silencing FKBP4 suppressed glucose uptake, lactic acid production and18F-FDG uptake compared with the control group. Mechanistically, our funding indicated that FKBP4 participates in glycolysis through p53 mediated HK2 signaling pathway, specially, FKBP4 knockdown promotes the expression and stability of p53 protein rather than affecting the transcription level. Finally, rescue experiments revealed that simultaneous knockdown of both FKBP4 and p53 partially reversed the inhibitory effects on HK2 protein levels and18F-FDG uptake. Our study elucidates a novel role of FKBP4 in promoting HCC development and glycolysis by modulating the p53/HK2 signaling pathway. Given the critical role of aerobic glycolysis in the progression of HCC, targeting FKBP4 may offer a new therapeutic strategy for treating this malignancy.

Integration of single-cell and spatial transcriptome sequencing identifies CDKN2A as a senescent biomarker in endothelial cells implicating hepatocellular carcinoma malignancy.

Highly complex tumor microenvironment makes hepatocellular carcinoma (HCC) as one of the most malignant tumors worldwide. The role of cellular senescence in HCC has been gradually recognized. The present study aimed to comprehensively elucidate the senescence-related features of HCC in single-cell and spatial dimension. Single-cell RNA sequencing (scRNA-Seq) data was used to clarify the heterogeneity of senescence-related genes (SRGs) among multiple cell types within HCC. Spatial transcriptome RNA sequencing (stRNA-Seq) data was used for depicting SRGs features in spatial dimension. A prognostic model based on SRGs was constructed by using of bulk sequencing (bulk-Seq) data of HCC. The cell-cell interaction of senescent endothelial cells (ECs) in tumor microenvironment was analyzed. Then, the role of senescent ECs was verified through in vitro and in vivo experiments. The level of senescence demonstrated substantial heterogeneity among different cell types within tumor microenvironment of HCC, where ECs exhibited the most prominent senescent phenotype. Senescent ECs activated specific regulatory pathways through communicating with other cell types, with a potential impact on tumor progression. Spatial analysis revealed senescent ECs mainly located in the core region of HCC. The interaction of senescent ECs and immune cells implicated their role in tumor progression and immunotherapeutic response. In addition, CDKN2A was identified as an independent risk factor for HCC prognosis by constructing a prognostic model. Patients with high risk displayed an even worse outcome. The experimental verification indicated senescence of ECs determined by CDKN2A exhibited a secretory phenotype. Furthermore, senescent ECs with CDKN2A overexpression promote the proliferation and migration of HCC. The present study recognizes the critical effect of senescent ECs defined by CDKN2A in the promotion of tumor progression, which sheds new light on the investigation of ECs senescence in HCC.

CAR-T cell therapy for hepatocellular carcinoma: current trends and challenges

Hepatocellular carcinoma (HCC) ranks among the most prevalent cancers worldwide, highlighting the urgent need for improved diagnostic and therapeutic methodologies. The standard treatment regimen generally involves surgical intervention followed by systemic therapies; however, the median survival rates for patients remain unsatisfactory. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a pivotal advancement in cancer treatment. Both clinical and preclinical studies emphasize the notable efficacy of CAR T cells in targeting HCC. Various molecules, such as GPC3, c-Met, and NKG2D, show significant promise as potential immunotherapeutic targets in liver cancer. Despite this, employing CAR T cells to treat solid tumors like HCC poses considerable challenges within the discipline. Numerous innovations have significant potential to enhance the efficacy of CAR T-cell therapy for HCC, including improvements in T cell trafficking, strategies to counteract the immunosuppressive tumor microenvironment, and enhanced safety protocols. Ongoing efforts to discover therapeutic targets for CAR T cells highlight the need for the development of more practical manufacturing strategies for CAR-modified cells. This review synthesizes recent findings and clinical advancements in the use of CAR T-cell therapies for HCC treatment. We elucidate the therapeutic benefits of CAR T cells in HCC and identify the primary barriers to their broader application. Our analysis aims to provide a comprehensive overview of the current status and future prospects of CAR T-cell immunotherapy for HCC.

Impact of IL-8 on survival after TARE in HCC: a comprehensive investigation and external validation from the SORAMIC trial.

In the treatment of hepatocellular carcinoma (HCC) with transarterial radioembolization (TARE), identifying reliable biomarkers for predicting survival outcomes remains a critical challenge. We aimed to address this gap by investigating the significance of serum cytokines associated with inflammation as potential biomarkers for the selection of patients for TARE. Our retrospective study involved 161 patients diagnosed with HCC who underwent Y90 radioembolization at our medical center between 2010 and 2020. Serum samples from a subset of 78 patients were retrospectively analyzed to determine the concentrations of pro-inflammatory cytokines. The results from the prospective SORAMIC trial were used for independent validation. With a median overall survival of 36 weeks (range 4-436), our study showed the strongest correlation between 12-week survival and IL-8 levels before treatment (p < 0.001), while other relevant interleukins, interferon-α2, INF-γ, TNF-α and MCP-1 were not associated with survival. IL-8 levels below the cut-off of 190 pg/mL were significantly associated with increased 12-week and 24-week survival, with hazard ratios of 19.01 (95% CI: 2.29-157.89) and 2.57 (95% CI: 1.05-6.31), respectively (p = 0.006 and p = 0.039, respectively). In the adjusted multivariate analysis, the 190 pg/mL cut-off for IL-8 remained independently associated with 12- (p = 0.011) and 24-week survival (p = 0.039). Similarly, the SORAMIC population showed a strong association between IL-8 levels and 36-week survival (p = 0.03). Our study emphasizes the pivotal role of IL-8 as a valuable parameter, demonstrating its potential for predicting treatment outcomes and assessing liver function in patients with HCC undergoing TARE. The robustness of these findings warrants further validation.

Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinoma.

Microvascular invasion (MVI) is an independent risk factor of poor prognosis in hepatocellular carcinoma (HCC) and can be used to guide the diagnosis and treatment of HCC. The immune system serves as an integral role in the incidence and progression of HCC. However, the molecular biology correlation between MVI and tumor immunity and the value of combining the two parameters to predict patient prognosis and HCC response to treatment remain to be evaluated. In this study, we used univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis to establish the MVI and immune-related gene index (MIRGPI) including eight genes. We demonstrated that the MIRGPI was an independent risk factor in predicting the prognosis of HCC. Subsequently, our research established a nomogram model combining pathologic characteristics and verified its good clinical application value. In addition, our study found that the TP53 gene had a higher mutation frequency and a lower degree of immune infiltration in the high-risk group. The low-risk group had higher sensitivity to immunotherapy, sorafenib, and TACE treatment, and the high-risk group had higher sensitivity to common chemotherapeutic agents. Finally, SEMA3C was found to facilitate the proliferation, migration and invasive ability of HCC by in vitro and in vivo experiments, and its mechanism may be associated with the activation of the NF-Κb/EMT signaling pathway. In summary, the MIRGPI signature we developed is a reliable marker for the prediction of prognosis and treatment response, and is important for the prognostic assessment and individualized treatment of HCC.

Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population.

Nonalcoholic fatty liver disease (NAFLD) has become a common health care burden worldwide. The high heterogeneity of NAFLD remains elusive and impairs outcomes of clinical diagnosis and pharmacotherapy. Several NAFLD classifications have been proposed on the basis of clinical, genetic, alcoholic, or serum metabolic analyses. Yet, accurately predicting the progression of NAFLD to cirrhosis or hepatocellular carcinoma (HCC) in patients remains a challenge. Here, on the basis of a Chinese cohort of patients, we classified NAFLD into three distinct molecular subtypes (NAFLD-mSI, NAFLD-mSII, and NAFLD-mSIII) using integrative multiomics including whole-genome sequencing (WGS), proteomics, phosphoproteomics, lipidomics, and metabolomics across a broad range of liver, blood, and urine specimens. We found that NAFLD-mSI had higher expression of CYP1A2 and CYP3A4, which alleviate hepatic steatosis through mediating free fatty acid/bile acid-mTOR-FXR/PPARα signaling. NAFLD-mSII displayed an elevated risk of liver cirrhosis along with increased hepatic infiltration of M1 and M2 macrophages because of lipid-triggered hepatic CCL2 and CRP production. NAFLD-mSIII exhibited a potential risk for HCC development by increased transcription of CEBPB- and ERCC3-regulated oncogenes because of activation of the EGF-EGFR/CHKA/PI3K-PDK1-AKT cascade. Next, we validated the existence of these three NAFLD molecular subtypes in an external cohort comprising 92 patients with NAFLD across three different Chinese hospitals. These findings may aid in understanding the molecular features underlying NAFLD heterogeneity, thereby facilitating clinical diagnosis and treatment strategies with the aim of preventing the development of liver cirrhosis and HCC.

The ncRNA-AURKA Interaction in Hepatocellular Carcinoma: Insights into Oncogenic Pathways, Therapeutic Opportunities, and Future Challenges

Hepatocellular carcinoma (HCC) represents a major public health concern and ranks among the leading cancer-related mortalities globally. Due to the frequent late-stage diagnosis of HCC, therapeutic options remain limited. Emerging evidence highlights the critical role of non-coding RNAs (ncRNAs) in the regulation of Aurora kinase A (AURKA), one of the key hub genes involved in several key cancer pathways. Indeed, the dysregulated interaction between ncRNAs and AURKA contributes to tumor development, progression, and therapeutic resistance. This review delves into the interplay between ncRNAs and AURKA and their role in hepatocarcinogenesis. Recent findings underscore the involvement of the ncRNAs and AURKA axis in tumor development and progression. Furthermore, this review also discusses the clinical significance of targeting ncRNA-AURKA axes, offering new perspectives that could lead to innovative therapeutic strategies aimed at improving outcomes for HCC patients.

Correspondence on Letter regarding "Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis".

Correspondence on Letter regarding "Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis".

Edge computing-based ensemble learning model for health care decision systems.

A growing number of humans have suffered severe chronic illnesses, which has caused a boost in the requirement for diagnostic and medical treatment procedures that are both accurate and fast. Improved patient conditions and enhanced Decision-Making Systems (DMS) for healthcare professionals are the primary objectives of the Clinical Decision Support System (CDSS) recommended in this research article. The main drawback of traditional Machine Learning (ML) techniques is their failure to predict reliably. To solve this problem, the proposed model creates an Ensemble Extreme Learning Machine (EN-ELM) algorithm that combines predictors trained on several different data sets. This lowers the chance of overfitting. The suggested CDSS uses many different data processing methods, including Adaptive Synthetic (ADASYN) and isolation Forest (iForest), which fix problems like outliers and class imbalance. This approach significantly enhances the framework's classification performance. Also, the CDSS is compatible with an EC model, which enables real-time computation while minimizing the requirement for integrated systems. The recommended CDSS applies iForest and ADASYN to execute large-scale trials validating high standards of accuracy across numerous datasets. Researchers concluded that a suitable ELM classification threshold of 85% is the most effective, which substantially boosts the accuracy of the predictive model. When applied to various medical datasets, such as Hepatocellular Carcinoma (HCC), Cervical Cancer, Chronic Kidney Disease (CKD), Heart Disease, and Arrhythmia, the EN-ELM achieved accuracy rates of 99.36%, 98.15%, 97.85%, 97.06%, and 96.72%, respectively. By measuring this progress, the CDSS could dramatically improve the accuracy of chronic illness diagnosis and treatment, which similarly affects clinicians.

Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma.

Metabolic dysfunction-associated steatotic liver disease (MASLD) asscociated hepatocellular carcinoma (HCC) is becoming a growing concern in global healthcare. The early-life gut microbiota plays a crucial role in maintaining healthy. However, the impact of early-life gut microbiota dysbiosis on the advancement of MASLD-HCC remains inadequately understood. In the present study, we investigated the role of early-life gut microbiota in the development of MASLD-HCC in streptozotocin and high-fat diet (STZ-HFD) induced mouse model. We recorded the body weight and lifespan, and dynamically monitored the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (T-CHO) and blood glucose in the serum monthly. In addition, we examined various immune cells present in the liver, such as T cells, B cells, NK cells, NKT cells, αβT cells, γδT cells, macrophage and MDSC cells by flow cytometry and conducted liquid chromatography mass spectrometry (LC-MS) based analysis on liver tissue from control and early-life antibiotic exposure mice (early-Abx) MASLD-HCC mice. We found that early-Abx mice suffered from more severe tumor burden and further confirmed that hepatocytes and immune cells were all disturbed. Importantly, early-life antibiotic exposure alters the liver metabolic profiling especially glycerophospholipids and lipid accumulation. Furthermore, mice exposed to antibiotics in early-life showed disturbances in glucose metabolism and developed insulin resistance. Collectively, our findings revealed that early-life antibiotic exposure accelerated the progression of MASLD-HCC by impairing the hepatocytes, immune homeostasis and metabolites persistently, highlighting the importance of the early-life microbiota in the development of MASLD-HCC.