Search Results (1,392)

Hantavirus cardiopulmonary syndrome (HCPS) caused by Andes Orthohantavirus (ANDV) carries case-fatality rates up to 40%; however, the innate immune determinants of disease severity remain poorly defined. Natural killer (NK) cells are central mediators of early antiviral immunity, but their landscape during the earliest phase of ANDV infection has not been characterized. Using multiparameter flow cytometry and unsupervised UMAP-based clustering in PBMCs from 13 HCPS patients stratified by severity and nine healthy donors, we show that severe HCPS is characterized by a coordinated disruption of the CD56dim NK cell compartment, encompassing reduced subset frequencies, specific reduction in the terminally differentiated NKG2C+CD57+ adaptive-like pool, and intrinsic impairment of IFN-γ production and degranulation, deficits that were absent in mild patients and persisted in part beyond clinical recovery. Furthermore, CD56dimCD16+ NK cell frequencies correlated negatively with viral load across all acute patients, independent of clinical severity. These findings establish severe HCPS not merely as a state of NK cell depletion, but as one of selective functional impairment of the most cytotoxically competent NK cell population during the critical early acute phase of ANDV infection. Full article

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are characterized by substantial biological heterogeneity and complex regulation of apoptosis, metabolism, and angiogenesis. The aim of this study was to evaluate the concentrations of selected proteins: FGF2, HGF, Fas/CD95, CASP9, ALDH1A1, and GLUT1 in tumor and margin samples and assess correlations with clinical and demographic parameters. A total of 59 samples from patients with GEP-NETs were analyzed using multiplex immunoassay and ELISA methods. Significant differences in protein expression between tumor and margin tissues were observed. Fas/CD95 levels were lower in tumor samples, whereas HGF concentration was higher. Elevated HGF, FGF2 and Fas/CD95 levels were associated with advanced tumor stage. HGF and GLUT1 concentrations varied depending on nodal status, while FGF2, Fas/CD95, and CASP9 levels were increased in metastatic cases. Additionally, differences related to tumor localization and the influence of smoking and alcohol consumption were identified. Dysregulation of apoptotic, metabolic, and angiogenic pathways plays a crucial role in GEP-NETs progression and highlights the importance of the tumor microenvironment. GEP-NET exhibit biological heterogeneity and complex progression driven by multiple interacting molecular pathways. The factors analyzed may have potential significance as biomarkers of disease progression; however, their exact role requires further investigation in larger, prospective cohorts. Full article

Shallow groundwater systems of rural municipalities are highly vulnerable to long-term contamination from former on-site sanitation systems, while the hydrochemical response of the aquifer after sewerage network development may be delayed by several factors. In the present study, a total of 147 shallow groundwater samples collected during the summer sampling campaigns of 2018, 2019, 2023, and 2024 were analyzed for general water-quality parameters including pH, EC, NH₄⁺, NO₂⁻, NO₃⁻, PO₄⁻, Cl⁻, SO₄²⁻, microelements, and potentially toxic elements, including As, Pb, Cd, Ni, Cu, Zn, Fe, and Mn. The dataset was evaluated using descriptive statistics, Piper, Wilcox, and Gibbs diagrams, hierarchical cluster analysis, principal component analysis, and GIS-based spatial interpolation. The results indicate that, more than ten years after sewerage network development (2014), shallow groundwater in the study area still shows considerable contamination, primarily characterized by elevated mean concentrations of ammonium (0.836 mg/L), nitrate (177.43 mg/L), and chloride (313.26 mg/L), accompanied by high electrical conductivity (3115 µS/cm) and sodium enrichment (378.12 mg/L). Spatial and boxplot analyses of SAR further indicated increasing sodium-related heterogeneity after 2018, with higher local SAR values in 2023–2024. Hydrochemical diagrams revealed a shift towards Ca-Cl type to Na–Cl types, while multivariate analyses confirmed that salinity enrichment, nitrate contamination, water–rock interaction and redox-sensitive trace element mobilization act as overlapping but partly separable controls. The nitrate–chloride source plot indicated mixed contamination origins, dominated by residual sewage influence and manure-related inputs, with diffuse agricultural nitrogen leaching. Arsenic was used as a supporting indicator of mixing with wastewater; however, As was no longer detectable in most of the investigated wells, suggesting a marked reduction in the former wastewater leakage. These results support the slow attenuation of contamination in the shallow groundwater system affected by former wastewater infiltration and highlight the need for continuous monitoring. Full article

Estuaries along South Africa’s coastline are increasingly subjected to anthropogenic pressures that disrupt their biogeochemical function and increase the risk of contamination. This study presents the first seasonal assessment of heavy metal contamination and water quality indices in the Qholora Estuary, Eastern Cape Province. Surface water samples collected during wet and dry seasons were analysed for physicochemical properties and heavy metals (As, Cd, Cu, Fe, Hg, and Pb). Multiple pollution metrics (Pollution Index (PI), Nemerow Pollution Index (NPI), Heavy Metal Evaluation Index (HEI), Heavy Metal Pollution Index (HPI)), ecological risk indices ((Ecological Risk Index (ERI), and Potential Ecological Risk Index (PERI)), and the Water Quality Index (WQI) were applied and supported by Principal Component and Cluster Analyses to identify dominant pollutant, contamination sources and seasonal hydro-geochemical controls. Results reveal strong seasonal contrasts: wet-season conditions showed elevated ionic concentrations and enhanced mobilisation of Cu, Pb, Cd, Hg, and Fe due to storm-driven runoff and sediment resuspension, while dry-season patterns reflected evapo-concentration, prolonged residence times, and pH-mediated metal partitioning. Across indices, heavy metal contamination remained low in the dry season but increased significantly in the wet season, especially for Hg, which posed moderate to considerable ecological risk at most sites, indicating emerging ecological pressure under high-flow conditions. These findings highlight a generally low risk under average conditions but a pronounced seasonally vulnerable estuarine system, underscoring the need for intensified monitoring during periods of increased runoff. The study establishes an important baseline for regional water resource management. Full article

Pancreatic ductal adenocarcinoma (PDAC) is increasingly recognized as a systemic malignancy, characterized by profound alterations in tumor–host interactions. Small extracellular vesicles (sEVs) in peripheral blood may reflect these alterations and represent a promising minimally invasive source of biomarker information. In this proof-of-principle study, plasma-derived sEVs from patients with PDAC, healthy controls, and a comparative cohort with neuroendocrine lung cancer (NLC) were isolated by differential ultracentrifugation and characterized by western blotting and nanoparticle tracking analysis. Surface marker profiling was performed using the MACSPlex EV Kit IO, followed by univariate, multivariate, and machine-learning-based analyses. PDAC samples exhibited a distinct sEV immunophenotype with coordinated enrichment of angiogenesis-related markers (including CD105 and CD146), immune-regulatory markers (including CD25 and CD40), the coagulation-related marker CD142 and the invasion-associated marker MCSP. Principal component analysis, hierarchical clustering, and Random Forest classification showed exploratory separation of PDAC patients from healthy controls and NLC, supporting the presence of disease-specific vesicle surface marker patterns. In a very small subset of paired samples, descriptive longitudinal analyses illustrated measurable intra-individual changes during chemotherapy. Plasma sEV immunophenotyping is a technically feasible approach for capturing systemic disease-associated alterations in PDAC and provides a foundation for future biomarker-oriented validation studies. Full article

Neuroblastoma is characterized by frequent involvement of bone marrow (BM) as a site of cell dissemination and spread. In this study, single-cell RNA sequencing (scRNA-seq) was used to analyze the cellular heterogeneity of a subset of metastatic BM samples collected at initial diagnosis. Comparison of the single-cell data with bulk RNA sequencing further refined the analysis. An enrichment of regulatory T cells relative to a healthy control and activation of the CD24, CD47, and CD200 “don’t eat me” signals were documented. Computational analyses highlighted communication between neuroblastoma and myeloid cells via the amyloid precursor protein (APP) and midkine (MK) signaling networks. Within neuroblastoma cells, mutually exclusive adrenergic and transitory cell states were identified, and ten sub-clusters were denoted. In addition, common and unique tumor cell antigens were investigated. CNTFR and CHRNA3, as high-ranking candidates, were validated, confirming their strong selectivity for neuroblastoma cells. Taken together, these findings support the existence of a significant tumor-dependent modulation of the BM ecosystem, which should be considered when introducing immunotherapy. Furthermore, they highlight the potential to investigate new antigens at the single-cell resolution. Full article

Slaughterhouse wastewater introduces potentially toxic elements into aquatic ecosystems, yet bioaccumulation patterns in commercial fish species and associated human health risks remain underexplored in West Africa. This study quantified zinc (Zn), lead (Pb), iron (Fe), magnesium (Mg), chromium (Cr), and cadmium (Cd) in three ecologically distinct fish species—Oreochromis niloticus (Nile tilapia), Clarias gariepinus (African sharptooth catfish), and Mugil cephalus (Flathead grey mullet)—from two slaughterhouse-impacted rivers (Transamadi and Mgbuosimini) and a control site (Iwofe) in Rivers State, Nigeria. Metal concentrations were measured using atomic absorption spectrophotometry. Two-way ANOVA assessed species and location effects. Principal component analysis (PCA) was performed, with Mg used as a potential geogenic tracer, as its loading pattern was independent of Pb and Cd and consistent with the natural background. A Water Quality Index (WQI) classified Mgboshimini and Iwofe as having poor water quality (WQI > 75), while Transamadi had medium quality. Health risks were evaluated using estimated daily intake (EDI), target hazard quotients (THQ), and hazard indices (HI) following USEPA guidelines. Metal levels varied significantly by species and location (p < 0.001). Flathead grey mullet from Mgbuosimini had the highest Pb (1.50 ± 0.05 mg/kg) and Cd (0.41 ± 0.02 mg/kg), exceeding EU maximum levels for fish muscle (Pb 0.30 mg/kg, Cd 0.05 mg/kg) by 500% and 800%, respectively. PCA explained 77.5% of the variance, with Pb and Cd clustering as anthropogenic sources, while Mg loaded independently. THQ for Pb approached unity in Flathead grey mullet (0.88), and THQ for Cd reached 0.97. HI exceeded 1.0 in all species from Mgbuosimini, peaking at 2.07 in Flathead grey mullet. Uncertainty analysis (using ±SD) gave a HI range of 1.89–2.25 for this species, all above the safety threshold. Carcinogenic risk for Flathead grey mullet (3.97 × 10⁻⁴) approached the upper acceptable limit. Slaughterhouse effluent appears to elevate Pb and Cd burdens in fish, with detritivorous Flathead grey mullet posing the highest health risk. Exceedance of safety thresholds and HI > 1.0 indicate potential non-carcinogenic and carcinogenic risks. We recommend improved wastewater treatment and species-specific consumption advisories. Full article

Objective: Glutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy often presents as chronic focal epilepsy, usually with temporal lobe predominance, marked drug resistance, and inconsistent response to first-line immunotherapy. We assembled a large, harmonized, and literature-derived patient-level cohort to examine whether immunotherapy timing and regimen composition were associated with seizure outcome and to identify clinically meaningful prognostic signals. Methods: We performed a literature-derived patient-level analysis of 375 unique published cases linked to 132 contributory source publications from an audited full-text register of 166 reviewed studies. Descriptive analyses used the whole cohort. Treatment-response analyses assessed seizure outcome at the first evaluable post-immunotherapy assessment and at the last follow-up. Good seizure outcome was defined as seizure freedom and/or ≥50% seizure reduction. The primary timing comparison contrasted early treatment, defined as immunotherapy within 6 months of symptom onset, with late treatment, defined as immunotherapy after more than 12 months; four cases treated in the intermediate >6 to ≤12 month window were retained for descriptive timing summaries but excluded from the primary comparison. Statistical testing used the Fisher exact, Chi-square, Mann–Whitney U, and prespecified clustered logistic sensitivity analyses where appropriate. Results: The pooled phenotype was predominantly female, usually temporal-lobe-based, and frequently drug-resistant, with common autoimmune comorbidity and heterogeneous MRI abnormalities. Among timing-evaluable treated cases, earlier immunotherapy showed a class-specific, exploratory signal rather than a uniform regimen-independent effect. In rituximab/CD20-directed regimens, early treatment was associated with a higher rate of good seizure outcome than late treatment at both the first post-immunotherapy assessment and last follow-up (93.8% vs. 50.0%; risk difference [RD]: 43.8 percentage points; 95% CI: 7.7 to 72.7). A similar pattern was observed in the broader escalation group (94.4% vs. 55.6%; RD: 38.9 percentage points; 95% CI: 6.3 to 68.1). By contrast, steroid-containing regimens showed no clear early-versus-late advantage (84.6% vs. 88.2%; RD: −3.6 percentage points; 95% CI: −18.4 to 20.1). Shorter epilepsy duration before immunotherapy and absence of established drug resistance were the most clinically meaningful favorable baseline features. Significance: In GAD65 antibody-associated epilepsy, the therapeutic window may be most relevant for escalation strategies rather than for steroid-containing first-line regimens. However, these class-specific findings are exploratory and hypothesis-generating. They derive from non-randomized, literature-derived data and may reflect treatment intensity, center practice, publication era, and confounding by indication rather than isolated regimen superiority. Prospective collaborative registries with standardized longitudinal seizure outcome measures are needed to validate these observations. Full article

A fraction of the insulin-stimulated uptake of long-chain fatty acids (FAs) is mediated by the FA translocase cluster of differentiation 36 (CD36) in white adipocytes. Intracellular vesicle-localized CD36 is redistributed to the plasma membrane following insulin stimulation, enhancing the uptake of long-chain FAs across the plasma membrane. We previously developed an epitope-tagged CD36 reporter, which enabled the visualization and quantification of the plasma membrane translocation of CD36. Herein, we demonstrate that the insulin-stimulated CD36 translocation is regulated by the phosphoinositide 3-kinase (PI3K)/Akt2/Rac1/RalA axis in adipocytes of subcutaneous white adipose tissue (WAT) in living mice. The uptake of long-chain FAs by insulin was completely abrogated in white adipocytes isolated from adipocyte-specific rac1-knockout (adipo-rac1-KO) mice. Correspondingly, the translocation of CD36 to the plasma membrane by insulin was also totally inhibited in Rac1-deficient white adipocytes. PI3K and Akt2 acted upstream of Rac1, and the guanin nucleotide exchange factor FLJ00068 served as a regulator for Rac1. Furthermore, the involvement of another small GTPase RalA was suggested by inhibitory effects of a dominant-negative mutant. Taken together, these results support the notion that insulin regulates the plasma membrane translocation of CD36 by mechanisms similar to those for the translocation of the glucose transporter GLUT4 in white adipocytes. Full article

Renal-resident macrophages (RMs) are essential regulators of kidney homeostasis and repair, yet the mechanisms governing RM niche regeneration after acute depletion remain poorly defined. To overcome these limitations, we have developed an inducible human CD59- intermedilysin (hCD59-ILY) ablation system, enabling rapid, specific, and reversible depletion of targeted macrophage populations, and subsequent replenishment of RMs, followed by longitudinal scRNA-seq analysis of kidneys at baseline and days 1, 3, and 7 post-ablation. RM ablation triggered a rapid and sustained upregulation of Cx3cl1, predominantly in proximal tubular epithelial cells (PTC1/PTC2), establishing a persistent chemotactic niche signal that coincided with macrophage repopulation. Regenerating RMs transitioned from inflammatory/stress-associated states toward metabolically active and proliferative phenotypes enriched in glycolysis, oxidative phosphorylation, MYC, and cell-cycle programs, with attenuation of canonical inflammatory pathways. Cell–cell communication analysis revealed an early burst of intercellular signaling at day 1, followed by progressive normalization, with fibronectin (Fn1), osteopontin (Spp1), chemokine (Ccl), and amyloid precursor protein (App) axes emerging as key mediators of niche restoration. Transcriptional network analysis identified a conserved regulatory module (Tfe3, Mitf, Hif1a, Myc, Gabpa, Rcor1) coordinating macrophage differentiation and regenerative programming, linking metabolic adaptation to lineage reconstitution. Sub-clustering revealed five dynamically shifting RM subsets with distinct inflammatory, remodeling, proliferative, and surveillance states, reflecting a hierarchical regeneration process. Functional validation using clodronate-mediated depletion in Secreted Phosphoprotein 1 (Spp1) (Opn)-deficient mice demonstrated impaired macrophage repopulation, establishing osteopontin as a critical regulator of RM regeneration. Together, these data define a coordinated epithelial–immune circuit in which Cx3cl1-driven chemotaxis, Spp1-dependent signaling, and a core transcriptional network orchestrate macrophage niche reconstitution and kidney repair following acute immune cell ablation. Full article

This study presents an integrated computational framework for quantifying industrial impacts on marine ecosystems through the combined assessment of multiple environmental quality indices. The Aquatic Water Quality Index (AWQI) and four diagnostic pollution indices, namely the Heavy Metal Pollution Index (HPI), Metal Index (MI), Degree of Contamination (C_d), and Pollution Index (PI), were applied across 23 offshore sites in Mesaieed Industrial City, Qatar, to establish a high-resolution baseline for evaluating the effects of industrial effluents and brine discharge. Multivariate statistical analyses, including Principal Component Analysis (PCA) and Cluster Analysis (CA), identified Cr, Pb, Mn, Ni, and Zn as the principal drivers of water quality variability, effectively distinguishing anthropogenic influences from natural background conditions. To enable rapid and automated marine environmental assessment, three machine learning models—Artificial Neural Networks (ANN), Random Forest (RF), and Decision Trees (DT)—were developed and evaluated for predicting the investigated indices. Model performance was assessed through rigorous training–testing validation and the Diebold–Mariano test. The results demonstrated that model selection significantly influences predictive accuracy. Among the evaluated algorithms, RF achieved the highest predictive performance for AWQI (R² = 0.88) and C_d (R² = 0.92), whereas ANN performed best for HPI (R² = 0.89), and DT yielded the most accurate predictions for MI (R² = 0.82). Despite the index-specific strengths of individual models, RF emerged as the most robust and generalizable approach, consistently providing superior performance across heterogeneous environmental datasets. The proposed framework advances marine water quality assessment from conventional descriptive monitoring toward a proactive, data-driven paradigm, offering a scalable and cost-effective decision support tool for environmental management, pollution mitigation, and evidence-based coastal governance in industrialized coastal regions. Full article

Effectively integrating graph topology and node attributes, while assigning nodes with both semantic similarity and structural closeness to the same community, remains a key challenge in attributed graph community detection. To address this challenge, this study proposes TVHCL-CD, a two-view hierarchical contrastive learning-driven method for community detection. The proposed method constructs an attribute view and a modularity view from the node attribute matrix and the modularity matrix, respectively, to model attribute semantics and high-order community structure priors. Structure-aware two-view representations are then learned in parallel through dual-view graph attention encoders incorporating multi-order neighborhood priors. Furthermore, a structure-enhanced Graph Transformer fusion module is designed to achieve node-level adaptive fusion of the two-view representations by introducing a learnable adjacency bias into global self-attention and a view-aware gating mechanism into the feed-forward network. To align the optimization objective with community semantics, a hierarchical contrastive learning strategy is further developed. Specifically, view-level consistency contrastive learning constructs modularity-guided augmented views to improve representation robustness, while community-level semantic contrastive learning incorporates partial ground-truth labels to enhance intra-community compactness and inter-community separation. Finally, clustering is performed on the fused representations to obtain community partitions. Experimental results on eight real-world attributed graphs and the generated tree-like attributed graph Tree-2500 indicate that TVHCL-CD achieves competitive performance under the semi-supervised transductive setting, while ablation results support the contributions of its main components. Full article

Background: Dysregulated G protein-coupled receptor (GPCR) signaling is increasingly implicated as an important driver for oncogenesis. Uveal melanoma (UM) represents a highly metastatic intraocular malignancy primarily driven by activating mutations in G protein family members Gαq/11. Although Tebentafusp, the first FDA-approved bi-specific T-cell engager for UM, improves survival, its activity is restricted to specific human leukocyte antigen (HLA) alleles, highlighting the need to identify broadly expressed targetable proteins for immunotherapeutic strategies. Here we aimed to define surfaceome and phospho-signaling signatures associated with oncogenic Gαq-signaling. Methods: Heterologous and UM in vitro systems were used to interrogate Gαq-driven changes. HEK293T cells were transfected with wild-type Gαq or the oncogenic Gαq (R183Q) mutant, with surface marker profiles quantified by flow cytometry. Complementary immunophenotyping was performed in the Gαq-mutant UM cell line MP46 and Gα11-mutant line MP41. Kinase phosphorylation was assessed in control and Gαq mutant conditions followed by effect size estimation (Hedges’ g), Welch’s t-test, principal component analysis, and Spearman correlation-based network analysis of surface and phosphoprotein readouts. Results: Hyperactive Gαq in HEK293T cells induced graded remodeling of surface protein profiles, including reduced CD56 (NCAM) and CD49c (ITGA3) expression. Similarly, in UM models, MP46 versus MP41 had limited expression of CD56 and CD49c. Moreover, phospho kinase profiling and network analysis identified altered surface-phosphoprotein relationships, including a CD56-p70 S6 kinase association. Conclusions: These data provide new insights into Gαq-driven modulators of UM phenotype of relevance for studies of tumor–microenvironment interaction and metastasis. Full article

Background: Virological suppression is a key outcome of antiretroviral therapy. Despite progress in HIV treatment in Kazakhstan, virological non-suppression remains a relevant clinical and public health issue requiring further analysis. This study aimed to assess the prevalence of virological suppression (VS) and to identify factors associated with the absence of VS among people living with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy (ART) in Kazakhstan. Methods: A retrospective cross-sectional analytical study was conducted using secondary analysis of a de-identified national registry database of people living with HIV (PLHIV) receiving ART in the Republic of Kazakhstan as of 30 September 2025. The primary outcome was virological non-suppression (VNS), defined as the last viral load (VL) value of at least 200 copies per milliliter. The analysis included sex, age, presumed route of HIV transmission, the first available cluster of differentiation 4 (CD4) cell count recorded in the registry, the last recorded percentage category of adherence to ART, and the aggregated category of ART regimen. The main descriptive, bivariate, and multivariable analyses were performed using a complete-case approach. Independent associations were assessed using multivariable logistic regression, and the results were presented as adjusted odds ratios (aORs) with 95 percent confidence intervals (CIs). Results: The initial registry extraction included 33,614 records, of which 32,130 patients were included in the final analytical sample. VS was achieved in 29,454 (91.7%) patients, whereas VNS was observed in 2676 (8.3%) patients. In the multivariable model, higher adjusted odds of VNS were observed among men compared with women (aOR 1.14; 95% CI 1.02–1.26), as well as among patients with a first CD4 count < 200 cells/μL compared with those with a first CD4 count of ≥500 cells/μL (aOR 1.25; 95% CI 1.09–1.44). The strongest association was found for reduced adherence to therapy. Compared with adherence of at least 95%, the adjusted odds of VNS were markedly higher among patients with adherence of 85–94% (aOR 28.66; 95% CI 25.85–31.77) and among those with adherence below 85% (aOR 61.05; 95% CI 50.50–73.81). In all age groups older than 25 years, the adjusted odds of VNS were lower than among patients younger than 25 years. Lower adjusted odds of VNS were also observed among patients with homosexual transmission, vertical transmission, and other or unspecified transmission routes compared with heterosexual transmission. Among ART regimens, regimens containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) were associated with lower adjusted odds of VNS than dolutegravir-containing regimens (DTG-containing regimens) (aOR 0.68; 95% CI 0.52–0.88), whereas no statistically significant differences were identified for regimens containing protease inhibitors (PIs). Conclusions: Despite the high overall level of VS among PLHIV receiving ART in Kazakhstan, VNS remains concentrated in clinically and programmatically important subgroups. It was most strongly associated with reduced adherence and was also associated with younger age, marked baseline immunosuppression, and male sex in the primary model. These findings support the need for targeted interventions focused on adherence support, early diagnosis, and differentiated long-term follow-up of patients. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is challenging to treat with chemotherapy. Immunotherapy has shown moderate responses in inflammatory and immunosuppressive tumor environments. Hepatic cytochrome P450 monooxygenases (CYPs) play a crucial role in xenobiotic and drug metabolism, as well as lipid and steroid metabolism. We aimed to investigate whether CYP expression and various parameters of the innate and adaptive immune system are prognostic factors for the survival of HCC patients. Methods: HCC biopsies (n = 370) from The Cancer Genome Atlas (TCGA) database were analyzed using Kaplan–Meier statistics and the KMPlotter algorithm. Parameters such as immune cell infiltration, DNA mutation rates, and neoantigen load were selected for survival analysis and subjected to hierarchical cluster analysis. The expression of candidate CYP genes in tumors was compared to that in normal liver tissues. Furthermore, tumor infiltration of innate immune cells (basophilic and eosinophilic granulocytes, natural killer cells), adaptive immune cells (CD4+ memory and CD8+ cytotoxic T cells, regulatory T cells, type 1 and type 2 helper T cells), and mesenchymal stem cells was examined. Results: High expression of CYP19A1 and CYP26B1 was associated with shorter survival, whereas high expression of CYP3A5, CYP3A43, CYP7A1, and CYP27A1 was linked to longer survival. Mutation rates combined with CYP expression showed a correlation with five out of six CYP genes, while a high neoantigen load produced less definitive results. A specific cluster exhibiting high CYP expression and immune cell counts or mutation/neoantigen rates was associated with shorter survival, while another cluster was linked to longer survival. Conclusions: CYPs involved in the metabolic regulation of HCC, including CYP3A5, CYP3A43, CYP7A1, CYP19A1, CYP26B1, and CYP27A1, were found to have prognostic value for patient survival. Combined signatures that include CYP expression, mutational rates, and immune cell infiltration into tumors further enhanced the prognostic value for patient survival. This suggests that CYPs may influence the creation of a tumor-specific metabolic microenvironment that impacts immune functions. These combined signatures could be utilized for patient stratification to personalize tumor treatment and develop novel combination therapies aimed at optimizing treatment outcomes, such as combining transarterial chemoembolization (TACE) with immune checkpoint inhibitors. Full article