Journal of Hepatocellular Carcinoma最新文献

Background: The influence of pyroptosis on tumors is complex and diverse. However, its specific impact on hepatocellular carcinoma (HCC) is still not well understood. Therefore, the objective of this study was to develop a prognostic signature for HCC based on pyroptosis-related genes.

Methods: The single-cell RNA sequencing (scRNA-seq) data, mRNA expression files and corresponding clinical information of HCC were obtained from the The Cancer Genome Atlas and Gene Expression Omnibus databases. Python was used to process scRNA-seq data and calculated the enrichment score of pyroptosis-related genes (PRGs). Weight Co-Expression Network Analysis was used to identify pyroptosis-related hub genes. By overlapping the PRGs from scRNA-seq analysis and bulk RNA-seq analysis, respectively. Then, Univariate cox and LASSO regression were used to construct the pyroptosis prognostic model. Multivariate cox was used to identify independent factors for HCC and then developed a nomogram. The biological functions, survival analysis, immune characteristics, therapy response, and m6A modification status were analyzed.

Results: Based on the scRNA-seq analysis and bulk RNA-seq analysis, hub PRGs were identified in HCC. Of those genes, five PRGs (ADGRE2, FCER1G, SLC9A9, CYBB, SLAMF6) were selected as a prognostic signature. The risk score established from the prognostic signature was an independent prognostic factor for HCC. The high-risk score group is associated with a poor prognosis, characterized by immunosuppressive features.

Conclusion: This study uniquely integrates single-cell and bulk transcriptomic data to systematically identify pyroptosis-related prognostic biomarkers, pinpointing their cellular origin within the tumor microenvironment.

Objective: This study aims to compare the efficacy and safety of transarterial chemoembolization (TACE) and radio-frequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) within the Milan criteria.

Materials and methods: 162 patients with HCC who underwent TACE (n=97) or RFA (n=65) from February 2011 to December 2024. A matched cohort composed of 88 patients was included after propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and safety.

Results: Baseline characteristics were balanced between the two groups after propensity score matching. Before matching, the 1-, 3-, and 5-year OS rates were 71.0%, 48.7%, 34.1%, respectively, in the TACE group and 87.0%, 69.5%, 63.1%, respectively, in the RFA group (P = 0.006). The 1-, 2-, and 3-year PFS rates were 37.1%, 25.1%, 18.3% in TACE group, and 52.6%, 43.3%, 40.6% in RFA group (P=0.009). After matching, the 1-, 3-, and 5-year OS rates were81.2%, 48.1%, 37.1%, respectively, in the TACE group and 88.6%, 65.6%, and 54.6%, respectively, in the RFA group (p=0.15). The 1-, 2-, and 3-year PFS rates were 33.3%, 20.5%, 17.5% in TACE group, and52.3%, 40.2%, 37.8% in RFA group (P=0.036). Before and after PSM, the incidence of major complications (before PSM P=0.306, after PSM P=0.08) and length of hospital stay (before PSM P=0.25, after PSM P=0.406) were similar between the two groups.

Conclusion: In the treatment of HCC within the Milan criteria, RFA demonstrated a superior median PFS compared to TACE, although there was no significant difference in OS between the two therapies.

Objective: This study aimed to evaluate the clinical efficacy and safety of combined therapy (transcatheter arterial chemoembolization [TACE] with hepatic artery infusion chemotherapy [HAIC] combined with tyrosine kinase inhibitors [TKIs] and PD-1 inhibitors) versus TACE alone in hepatocellular carcinoma (HCC) patients with concurrent portal/hepatic vein tumor thrombus (PVTT/HVTT) and arteriovenous fistula (AVF).

Materials and methods: This single-center retrospective study analyzed 301 HCC patients with PVTT/HVTT and AVF who received either combined therapy (n=177) or TACE monotherapy (n=124). Propensity score matching (PSM) was used to minimize confounding bias, yielding an average of 109 patients per group. Key outcomes compared included tumor thrombus regression rate, AVF closure rate, objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), and adverse events (AE).

Results: After PSM, the AVF complete closure rate of the combination therapy group was significantly higher than the TACE group (63.3% vs 27.5%, p < 0.001). According to response evaluation criteria in solid tumors (RECIST) 1.1 criteria for tumor thrombus response, the combination therapy group showed higher ORR (47.7% vs 7.3%, p < 0.001) and DCR (73.4% vs 50.5%, p < 0.001) than the TACE group. The combined therapy provided longer mOS (16.70 vs 10.40 months, p < 0.0001) and mPFS (14.23 vs 8.21 months, p < 0.0001) than TACE. The incidences of grade 3/4 AE were similar in both groups, respectively, 37.6% and 33.9%, p = 0.57.

Conclusion: Compared with TACE monotherapy, the combined therapy is a promising option with acceptable safety for HCC patients with PVTT/HVTT and AVF.

Purpose: This study aims to elucidate the anti-tumor properties of rutin and its specific molecular mechanisms for inhibiting hepatocellular carcinoma (HCC) through the ferroptosis.

Methods: The effects of rutin on HuH-7 cell proliferation, migration, invasion, and cell cycle progression were evaluated through in vitro experiments. By integrating bioinformatics analysis and network pharmacology, potential ferroptosis targets influenced by rutin in HCC were identified from the TCGA-LIHC database. A prognosis-related risk-scoring model was constructed and validated in the GEO14520 cohort and ICGC-LIRI-JP. Samples were categorized into high-risk and low-risk groups based on their scores. Enriched pathways within these different risk groups were explored using Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). Additionally, key targets of rutin-related ferroptosis in HCC cells were investigated through single-cell analysis and molecular docking studies.

Results: Rutin inhibited the proliferation, invasion, migration, and cell cycle progression of HCC cells in a dose-dependent manner. We constructed a risk model comprising five ferroptosis-related targets of rutin (FRTs-R): ACACA, AKR1C3, ALDH2, AR, and CDK1. This prognostic model was validated in the GEO14520 and ICGC datasets, revealing that the low-risk group had a better prognosis than the high-risk group. Furthermore, lipid metabolism pathway activity was up-regulated in the low-risk group. Single-cell analysis indicated specific expression of AKR1C3 in HCC cells, while molecular docking analysis showed that, among the five potential targets, AKR1C3 demonstrated the most stable binding affinity to rutin.

Conclusion: Our findings suggest that rutin may modulate ferroptosis in HCC, with rutin associated ferroptosis genes implicated in disease biology; moreover, the proposed risk scoring model shows promising prognostic utility in HCC.

Purpose: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide and is particularly prevalent in Taiwan. While curative treatments offer favorable outcomes for early-stage HCC, prognostic factors change and option medical strategy remain uncertain in long term survival early-stage HCC.

Patients and methods: This retrospective study analyzed 1144 patients with BCLC stage 0 or A HCC from a cancer registry (2011-2020) followed through 2023. Prognostic factors were evaluated using Cox regression. Subgroup analyses were performed on patients who survived over five years, and further stratified into 5-10 years and >10 years survival groups to assess treatment outcomes and tumor-free status (TFS).

Results: Age >65, Child-Pugh B, and non-curative treatment were consistent poor prognostic factors; HBV-related HCC was associated with improved survival. Among patients surviving >10 years, higher TFS rates and lower stage progression were observed compared to those surviving 5-10 years. Curative treatment significantly increased the likelihood of achieving TFS (p = 0.044).

Conclusion: Long-term survival in early-stage HCC is influenced by age, liver function, viral etiology, and treatment strategy. Curative treatments significantly improve outcomes, and maintaining curative treatment options is crucial for patients who experience recurrence while still in the early stage of HCC.

Purpose: To evaluate whether radiomic features from contrast-enhanced computed tomography (CECT) of peritumoral regions can be used to preoperatively predict proliferative hepatocellular carcinoma (PHCC).

Patients and methods: Preoperative CT scans from 486 patients with hepatocellular carcinoma (HCC) were retrospectively analyzed and split into training (n = 252), testing (n = 109), and validation (n = 125) cohorts. Radiomic features were extracted from intra- and peritumoral regions (peri-3 mm, peri-5 mm, and peri-10 mm) on arterial phase (AP) and portal venous phase (PVP) images using PyRadiomics. Features were selected with LASSO regression and 10-fold cross-validation, and a radiomics score (Radscore) was calculated as a weighted sum of selected features. Patients were classified into high- and low-risk groups using the optimal Youden's index cutoff. Recurrence-free survival (RFS) was analyzed with Kaplan-Meier curves, feature contributions were quantified using SHapley Additive exPlanations (SHAP), and model performance was assessed by area under the curve (AUC).

Results: The Naive Bayes model using peri-5 mm features achieved the highest mean AUC (0.739) and accuracy (0.802), with AUCs of 0.839 and 0.639 in internal and external validation. In the test set, combining intra- and peritumoral features improved the AUC to 0.849 (95% CI: 0.773-0.924; sensitivity: 0.974; specificity: 0.606). In the validation set, AP, PVP, and their combined models achieved AUCs of 0.699, 0.672, and 0.695, respectively. SHAP highlighted in the Naive Bayes model that the increased inhomogeneity of the texture grayscale of the peritumoral tissue in the PVP may be associated with more aggressive HCC subtypes. Multivariable analysis identified rim-APHE (OR = 22.667), mosaic architecture (OR = 5.904), and intratumoral hemorrhage (OR = 4.897) as independent risk factors for PHCC (all p < 0.05). PHCC showed significantly worse RFS than non-PHCC (p < 0.0001). Radscore effectively stratified early recurrence risk (p < 0.0001).

Conclusion: Radiomic analysis of intratumoral and peri-5 mm enhancement features enables accurate preoperative PHCC identification and may inform intensified postoperative surveillance and adjuvant therapy.

Purpose: This study aimed to investigate the predictive value of the Tumor Burden Score (TBS) combined with Serum Prealbumin (PALB) and the Neutrophil-to-Lymphocyte Ratio (NLR) for the long-term prognosis of patients with unresectable hepatocellular carcinoma (uHCC) following transcatheter hepatic artery chemoembolization (TACE) therapy, and to elucidate its significance in guiding treatment planning.

Patients and methods: Clinical data from 940 patients with unresectable HCC who underwent TACE treatment at three hospitals in the Jiangsu Province between 2007 and 2018 were retrospectively analyzed. TBS was calculated using the formula: TBS² = (maximum tumor diameter)² + (number of tumors)² (The diameter of the tumor is measured in centimeters). The optimal cutoff values for TBS and NLR were determined using R software. Patients were risk-stratified based on their TBS-PALB-NLR (TPN) score. Independent predictors associated with survival were identified using univariate and multivariate Cox proportional hazards regression analyses.

Results: Independent risk factors identified through univariate Cox analysis included age, cirrhosis, ascites, BCLC stage, vascular invasion, NLR, TBS, PALB, AFP, Bilirubin, AST, and ALT. Multivariate analysis revealed that BCLC stage, NLR, TBS, and PALB were significant independent risk factors affecting overall survival (P < 0.05). The TPN score was established based on TBS, PALB, and NLR, and patients were stratified into low-TPN, intermediate-TPN, and high-TPN groups.

Conclusion: The TPN score is a low-cost, readily available prognostic tool that can effectively risk-stratify patients with uHCC. It may guide personalized adjuvant therapy (eg, systemic therapy for high-risk patients), particularly in resource-limited medical centers.

Background and objective: During the disease course of patients with BCLC B/C hepatocellular carcinoma (HCC) receiving systemic therapy, approximately half of the patients will develop cachexia. Therefore, early identification of which patients are likely to develop cachexia is of crucial significance.This study aims to construct and validate a nomogram for predicting the risk of cachexia in this population based on common clinical parameters.

Patients and methods: This retrospective single - center study involved 906 patients managed at the Fifth Medical Center of Chinese PLA General Hospital from January 2020 to December 2023. Baseline clinical imaging data, biochemical indicators, and relevant clinical data of patients before systemic treatment were collected. All patients were followed up to record treatment regimens and document weight changes for cachexia diagnosis. The data were stratified into a training cohort and a validation cohort. In this study, LASSO regression alongside univariate and multivariate Logistic regression analyses were utilized to ascertain independent risk factors linked to cachexia occurrence, and further to construct and validate a diagnostic nomogram.

Results: This nomogram incorporates predictors such as patient age, maximum size of intrahepatic lesions, extrahepatic metastasis, neutrophil-to-lymphocyte ratio (NLR), and total bile acids, demonstrating good predictive performance. In the training and validation cohorts, its Harrell's concordance index (C-index) reached 0.865 (95% CI: 0.836-0.895) and 0.820 (95% CI: 0.768-0.871), respectively. Calibration curves demonstrated strong consistency between the nomogram's predicted outcomes and the actual measured values, and decision curve analysis (DCA) further substantiated its clinical applicability.

Conclusion: This nomogram shows good predictive performance and can effectively identify high-risk individuals, but it is limited by its single-center retrospective design and requires further verification and optimization through multicenter prospective studies.

Background: The Spiegel lobe, a distinct subdivision of the hepatic caudate lobe, is characterized by its unique anatomical position, with close proximity to major hilar vasculature and extrahepatic structures. Therapeutic intervention for Spiegel lobe lesions remains technically challenging, with no established treatment protocol currently available.

Case presentation: This study reports four cases of recurrent hepatocellular carcinoma (HCC) in the Spiegel lobe treated with conventional transarterial chemoembolization (c-TACE) followed by microwave ablation (MWA) via a transhepatic left lobe approach. Postprocedural imaging assessment confirmed complete response (CR) in all patients according to mRECIST criteria. During a mean follow-up period of 33.75 months (range: 31-37), three patients maintained disease-free status, whereas one patient developed intrahepatic recurrence at 19.2 months. This patient achieved CR after repeat TACE-MWA combined with adjuvant lenvatinib and tislelizumab therapy. The mean overall survival (OS) was 33.75 months (95% CI: 31.2-36.3).

Conclusion: The combination of transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) for treating recurrent hepatocellular carcinoma (HCC) in the Spiegel lobe was proven feasible in this series of studies, and demonstrated favorable efficacy and safety profiles.

Background: Hepatocellular carcinoma (HCC) is influenced not only by tumor burden but also by liver function and the extent of fibrosis. Although the albumin-bilirubin (ALBI) score and the fibrosis-4 (FIB-4) index are validated independent predictors, their combined prognostic impact has been insufficiently examined.

Methods: We retrospectively analyzed 307 patients with HCC diagnosed between 2002 and 2025. ALBI and FIB-4 scores were calculated at baseline, and a composite score was generated using the β-coefficients obtained from a multivariable Cox regression model, allowing each component to contribute proportionally to its prognostic weight (combined score = 0.503 × ALBI + 0.0576 × FIB-4). Patients were stratified using the median cutoff value (-0.95). Outcomes included overall survival (OS), event-free survival (EFS) for those undergoing locoregional therapies, and progression-free survival (PFS) for patients treated with systemic therapy.

Results: Median OS was 12.1 months. Patients with combined scores ≤-0.95 had superior OS (18.3 vs 6.8 months, p < 0.001), and the score remained an independent predictor of OS (HR 2.01, 95% CI 1.48-2.72, p = 0.001). In the locoregional therapy group, lower scores predicted improved EFS (16.4 vs 5.8 months,: HR:1.86; 95% CI:1.17-2.96; p=0.009). Among systemic therapy patients, the combined score independently predicted PFS (HR 1.70, 95% CI 1.21-2.41, p = 0.021).

Conclusion: The combined ALBI-FIB-4 score is an accessible and reproducible prognostic marker across therapeutic settings in HCC. By integrating measures of hepatic reserve and fibrosis, it provides additional prognostic granularity beyond tumor-centric staging systems. These findings highlight its potential utility in personalized risk stratification and warrant validation in prospective, multi-ethnic cohorts.