Purpose:This study aimed to identify factors influencing overall survival (OS) in patients with hepatocellular carcinoma (HCC) undergoing microwave ablation (MWA) and to develop and validate a nomogram for predicting 3‑, 5‑, and 8‑year OS. Materials and Methods:Data from 440 patients who received MWA at Beijing Ditan Hospital, Captical Medical University were analyzed using least absolute shrinkage and selection operator (LASSO) regression, random forest (RF), and multivariable Cox regression to identify independent prognostic factors. A prognostic nomogram was constructed and validated. OS was assessed using Kaplan-Meier curves. Results:The variables selected by both LASSO and RF were incorporated into a multivariable Cox regression model, which identified tumor number, tumor size, monocyte-to-lymphocyte ratio (MLR), white blood cell count (WBC), and diabetes as independent risk factors for OS. The predictive accuracy, reliability, and clinical utility of the model were confirmed through Harrell's concordance index (C-index), time-dependent area under the receiver operating characteristic curve (AUC) analysis, calibration curves, and decision curve analysis (DCA). Furthermore, risk stratification based on the model effectively differentiated patients into distinct prognostic subgroups. Conclusion:A nomogram based on LASSO-RF-Cox analysis was developed to predict OS in early-stage HCC patients after MWA. The model demonstrated acceptable predictive performance in internal validation, with moderate discriminative ability. This model may help identify high-risk individuals and facilitate clinical decision-making, particularly in primary care settings due to its simple and readily available predictors.
Weiguo Lu,1,* Ying Lu,2,* Yang Wang11Department of Clinical Laboratory, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Infectious Disease Prevention and Control, Guangzhou Center for Disease Control and Prevention (Guangzhou Health Inspection Institute), Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Wang, Department of Clinical Laboratory, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 16, Airport Road, Baiyun District, Guangzhou, Guangdong Province, 510405, People’s Republic of China, Email wangyang90611@gzucm.edu.cnPurpose: Primary liver cancer is a prevalent malignancy with a poor prognosis globally. Patients with advanced disease often undergo transarterial chemoembolization (TACE), yet simple and effective prognostic biomarkers are lacking. This study aimed to investigate the prognostic value of the serum creatine kinase isoenzyme MB to total creatine kinase (CK-MB/CK) ratio in patients with advanced primary liver cancer receiving TACE.Patients and Methods: A single-center retrospective cohort study was conducted, enrolling 158 patients between January 2021 and September 2024. Based on a CK-MB/CK ratio cutoff of 1, patients were categorized into an abnormal group (n=52) and a normal group (n=106). Comparative analysis of baseline characteristics, Kaplan-Meier survival analysis, and Cox proportional hazards regression modeling were performed to assess the relationship between the CK-MB/CK ratio and overall survival (OS).Results: Patients in the abnormal group exhibited lower body mass index (BMI), lower rates of previous hepatectomy, higher levels of tumor markers (including AFP and CEA), and poorer liver function indices compared to the normal group. Kaplan-Meier analysis revealed a significantly shorter OS in the abnormal group (median OS: 15.0 months vs 32.5 months, log-rank P < 0.001). Multivariate Cox regression analysis confirmed that an elevated CK-MB/CK ratio was an independent risk factor for OS, with a hazard ratio of 3.895 (95% confidence interval: 1.946– 7.79).Conclusion: This retrospective single-center study suggests that a CK-MB/CK ratio > 1 may serve as an independent and easily accessible marker of poor prognosis in patients with advanced liver cancer undergoing TACE. Further validation in larger cohorts is needed. This marker is cost-effective and readily available in routine clinical practice, showing potential for risk stratification. When combined with D-dimer, it may provide a practical tool for clinical prognostic stratification.Keywords: primary liver cancer, creatine kinase isoenzyme MB, transarterial chemoembolization, prognosis
Background:Prognostic stratification remains suboptimal in unresectable hepatocellular carcinoma (uHCC) treated with locoregional therapy (LRT) plus lenvatinib and PD-1 blockade. Existing staging systems insufficiently reflect host nutritional-immune status. Methods:We included a multicenter retrospective study including 347 patients with uHCC treated with LRT, lenvatinib, and a PD-1 inhibitor. Nine prognostic models were developed using Cox regression Model performance was evaluated using time-dependent AUC (tdAUC), calibration, and decision curve analysis (DCA). A nomogram was constructed for individualized survival prediction. Results:Median overall survival (OS) was 33.1 months (95% CI, 30.5-not reached) and median progression-free survival (PFS) was 10.2 months (95% CI, 9.0-12.6) in the overall cohort. The integrated model (incorporating tumor burden, ALBI grade, AFP, PNI) showed superior discrimination, with C-indices of 0.780 (training cohort) and 0.785 (validation cohort). The tdAUCs for OS and PFS were 0.892 and 0.807, respectively, in the training cohort and 0.861 and 0.819, respectively, in the validation cohort. Calibration plots demonstrated good agreement between predicted and observed 2-year OS in both cohorts. Risk stratification based on tertiles yielded significantly separated survival curves in both cohorts (all P<0.001). The nomogram achieved strong predictive accuracy, with 1-, 2-, and 3-year AUCs of 0.879, 0.808, and 0.787, respectively. Conclusion:PNI-integrated prognostic model provides robust risk stratification for uHCC patients receiving LRT combined with lenvatinib and PD-1 inhibitors, supporting individualized pre-treatment risk assessment.
Tong Wang,1,* Tianrun Yang,1,* Tianze Wang,1 Ziming Wang,1 Pinsheng Han,2 Yi Bai,3 Yamin Zhang31First Central Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 2School of Medicine, Nankai University, Tianjin, People’s Republic of China; 3Tianjin First Central Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yamin Zhang, Tianjin First Central Hospital, Tianjin, People’s Republic of China, Email 5020200824@nankai.edu.cn Yi Bai, Tianjin First Central Hospital, Tianjin, People’s Republic of China, Email baiyipumch@sina.comBackground: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, with limited reliable biomarkers for early diagnosis and prognosis. In this study, we explored the role of DCUN1D5, a potential biomarker, in HCC.Methods: We performed integrated bioinformatics analyses of publicly available HCC datasets, including TCGA, GEO, and ICGC, followed by in vitro experiments on HCC cell lines to validate our findings.Results: DCUN1D5 expression was significantly elevated in HCC tissues compared to normal liver tissues. High DCUN1D5 levels were associated with poor prognosis and advanced tumor stage in HCC patients. Additionally, bioinformatics analysis revealed a correlation between DCUN1D5 expression levels and both immune infiltration and immunotherapy response in hepatocellular carcinoma. Functional assays revealed that DCUN1D5 knockdown inhibited cell proliferation, migration, and invasion in HCC cells. Mechanistically, Enrichment analysis revealed significant correlations between DCUN1D5 and multiple biological pathways; specifically, we observed a negative correlation between the expression level of DCUN1D5 and fatty acid metabolism. Further cellular experiments demonstrated that knockdown of DCUN1D5 can induce accumulation of free fatty acids in hepatocellular carcinoma cells.Conclusion: In summary, our study identified DCUN1D5 as a potential biomarker for poor prognosis in HCC, high expression of DCUN1D5 are closely associated with tumor invasion and proliferation. Knockdown of DCUN1D5 was found to inhibit the proliferation, migration, and invasion of HCC cells and increases its free fatty acid accumulation. These studies suggest new possibilities for treatment strategies for HCC.Keywords: DCUN1D5, HCC, fatty acid metabolism, biomarkers, prognosis, immunotherapy
Woo-Hyoung Kang,1,2 Shin Hwang,1,2 I-Ji Jeong,1 Deok-Bog Moon,1 Dong-Hwan Jung,1,2 Gi-Won Song,1,2 Young-In Yoon,1 Tae-Yong Ha,1 Gil-Chun Park1, On behalf of the Korean Liver Cancer Study Group1Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Korean Liver Cancer Association, Seoul, KoreaCorrespondence: Shin Hwang, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea, Tel +82-2-3010-3930, Fax +82-2-3010-6701, Email shwang@amc.seoul.krBackground: A simplified prognostic model, the AFP–PIVKA-II (AP) score, was developed to predict outcomes after resection of hepatocellular carcinoma (HCC). Unlike the conventional ADV score, it relies only on serum biomarkers (AFP and PIVKA-II), excluding tumor size.Methods: This study included 2257 patients who underwent liver resection for HCC, using data from the Korea Liver Cancer Registry (2015– 2022). The AP score’s ability to predict overall survival (OS) and microvascular invasion (MVI) was evaluated and compared with radiologic and pathologic ADV scores.Results: Median preoperative AFP and PIVKA-II levels were 9.2 ng/mL and 62 mAU/mL. Increasing AP scores showed consistent association with worse OS (p < 0.001). Kaplan–Meier survival analyses using 1.0 log-, 2.0 log-, and 4.0 log-interval groupings consistently demonstrated a stepwise decline in OS with increasing AP score (all p < 0.001). At 4.0 log intervals, Harrell’s c-indices for OS prediction were 0.604 (AP score), 0.681 (radiologic ADV score), and 0.677 (pathologic ADV score). For MVI prediction, the areas under the ROC curve values were 0.705, 0.733, and 0.741, respectively. Although ADV score-based models performed better overall, the AP score showed acceptable predictive ability for post-resection patient survival.Conclusion: The AP score is a simple, biomarker-based tool for estimating survival after HCC resection. While less accurate than ADV score models, its convenience supports use in settings requiring rapid assessment.Keywords: hepatocellular carcinoma, resection, recurrence, microvascular invasion, tumor biology
Qi Zhang,1,2,* Lina Sun,1,* Jiangwei Ji,1,3,* Xiaoyan Ding,1,3 Jinglong Chen1,31National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinglong Chen, Department of Oncology, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshundong Street, Chaoyang District, Beijing, 100015, People’s Republic of China, Tel +86-13051423388, Email cjl6412@ccmu.edu.cn Xiaoyan Ding, Department of Oncology, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshundong Street, Chaoyang District, Beijing, 100015, People’s Republic of China, Tel +86-13811560276, Email dingxiaoyan198111@163.comPurpose: This study aimed to identify factors influencing overall survival (OS) in patients with hepatocellular carcinoma (HCC) undergoing microwave ablation (MWA) and to develop and validate a nomogram for predicting 3‑, 5‑, and 8‑year OS.Materials and Methods: Data from 440 patients who received MWA at Beijing Ditan Hospital, Captical Medical University were analyzed using least absolute shrinkage and selection operator (LASSO) regression, random forest (RF), and multivariable Cox regression to identify independent prognostic factors. A prognostic nomogram was constructed and validated. OS was assessed using Kaplan–Meier curves.Results: The variables selected by both LASSO and RF were incorporated into a multivariable Cox regression model, which identified tumor number, tumor size, monocyte-to-lymphocyte ratio (MLR), white blood cell count (WBC), and diabetes as independent risk factors for OS. The predictive accuracy, reliability, and clinical utility of the model were confirmed through Harrell’s concordance index (C-index), time-dependent area under the receiver operating characteristic curve (AUC) analysis, calibration curves, and decision curve analysis (DCA). Furthermore, risk stratification based on the model effectively differentiated patients into distinct prognostic subgroups.Conclusion: A nomogram based on LASSO–RF–Cox analysis was developed to predict OS in early-stage HCC patients after MWA. The model demonstrated acceptable predictive performance in internal validation, with moderate discriminative ability. This model may help identify high-risk individuals and facilitate clinical decision-making, particularly in primary care settings due to its simple and readily available predictors.Keywords: hepatocellular carcinoma, microwave ablation, nomogram, overall survival
Shucheng Yang,1,2,* Meng Liu,1,2,* Yongjie Zhou,3 Jinhong Zhao,4 Yongming Tan,1,2 Weijia Wang2,5,61Department of Radiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 2Clinical Research Center for Medical Imaging of Jiangxi Province, Nanchang, 330006, People’s Republic of China; 3Department of Radiology, Jiangxi Cancer Hospital, Nanchang, 330006, People’s Republic of China; 4Department of Radiology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 5Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 6Jiangxi Provincial Key Laboratory for Precision Pathology and Intelligent Diagnosis, Department of Pathology and Institute of Molecular Pathology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongming Tan, Weijia Wang, Clinical Research Center for Medical Imaging of Jiangxi Province, Nanchang, 330006, People’s Republic of China, Email ndyfy04394@ncu.edu.cn; ndyfy04509@ncu.edu.cnPurpose: Microvascular invasion (MVI) is an important determinant of postoperative recurrence in hepatocellular carcinoma (HCC) but is usually confirmed only after surgery. This study aimed to develop and externally validate a multiphase CT framework integrating dynamic vascular trajectory, spatial intratumoral heterogeneity, and deep imaging features for preoperative MVI prediction and exploratory prognostic stratification.Patients and Methods: This retrospective multicenter study included 405 patients with pathologically confirmed HCC: 198 in the development cohort and 207 in two independent external-validation cohorts. Clinical variables, static multiphase radiomics, Delta vascular trajectory features, three-dimensional intratumoral heterogeneity (3D-ITH)/habitat features, and Vision Transformer (ViT) features were extracted. All preprocessing, model fitting, and threshold selection were confined to the development cohort. A capacity-constrained multimodal Transformer was compared with clinical, single-modality, simple concatenation, and tree-based models.Results: The cohort included 148 MVI-positive and 257 MVI-negative patients according to the locked blinded multireviewer reference standard. In pooled external validation, Transformer fusion achieved an area under the curve of 0.941 (95% CI, 0.906– 0.969), sensitivity of 0.951, specificity of 0.754, accuracy of 0.831, negative predictive value of 0.960, and Brier score of 0.113. Corresponding AUCs were 0.957 and 0.934 in the two external cohorts. Delta-only and clinical models achieved pooled external AUCs of 0.793 and 0.675, respectively. High fusion-risk patients had poorer composite RFS/PFS than low-risk patients (hazard ratio, 2.05; 95% CI, 1.36– 3.08; P < 0.001).Conclusion: The proposed dynamic vascular heterogeneity-centered framework demonstrated high external discrimination for preoperative MVI prediction in HCC and provided exploratory stratification of the available composite RFS/PFS endpoint. Prospective validation and recalibration are required before clinical implementation.Keywords: delta radiomics, habitat imaging, vision transformer, multimodal fusion, external validation, recurrence-free survival
Purpose:A growing body of research indicates that Vacuolar Protein Sorting 45 (VPS45) is essential for the development of tumours and the advancement of cancer. Its biological role and expression profile in HCC are still mostly unknown, nevertheless. Materials and Methods:Using a variety of datasets, including the Tumour Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA), among others, we examined the existence and prognostic importance of VPS45. Functional enrichment analysis was employed to elucidate the potential mechanisms through which VPS45 may influence HCC. Additionally, we assessed the relationship between VPS45 expression and immune cell infiltration using single-sample gene set enrichment analysis (ssGSEA) and Estimation of Stromal and Immune cells in Malignant Tumour tissues using Expression data (ESTIMATE). The Tumor Immune Dysfunction and Rejection (TIDE) algorithm was leveraged to assess the sensitivity of predicted gene expression to immunotherapy. Utilizing assays including CCK-8, wound healing, and Transwell migration and invasion methods, we performed in vitro experiments on the MHCC-97H cell line to further investigate the biological significance of VPS45 in the progression of hepatocellular carcinoma (HCC). Results:According to our research, VPS45 expression is markedly elevated in HCC, and elevated VPS45 levels are associated with a worse prognosis for patients. Functional enrichment analysis showed that elevated VPS45 expression is closely linked to the activation of various oncogenic pathways. VPS45 silencing decreases HCC cell invasion, metastasis, and proliferation, according to in vitro investigations. Interestingly, it was shown that VPS45 levels showed a positive link with immunosuppressive cell populations and related genes, but a negative correlation with a number of anti-tumor immune cell types. Immunotherapy resistance is more common in patients with increased VPS45 expression. Conclusion:This study clarifies the biological role of VPS45 in hepatocellular carcinoma (HCC) and, through comprehensive database analyses combined with in vitro experiments, supports its potential as a diagnostic and predictive biomarker for HCC. In addition to its value for disease detection and prognosis, VPS45 may help predict patient response to immunotherapy.
Background:Although first-line triple therapy of programmed death-1 inhibitors plus lenvatinib and intra-arterial locoregional therapy has shown potential clinical benefit for unresectable hepatocellular carcinoma (HCC), it has not yet been established as a standard treatment. This real-world study evaluated the efficacy and safety of first-line combination therapy with nivolumab, lenvatinib, and intra-arterial locoregional therapy (including transarterial chemoembolization or hepatic arterial infusion chemotherapy) in this population. Methods:This retrospective study included untreated unresectable HCC patients who received nivolumab plus lenvatinib and intra-arterial locoregional therapy between 26 March 2020 and 17 October 2023. The outcomes included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results:A total of 52 patients were included, the majority of whom were <65 years (86.5%) and male (90.4%). Most patients had compensated liver disease, with 92.3% classified as Child-Pugh class A. The ORR was 69.2% (95% confidence interval [CI]: 54.9%-81.3%) per mRECIST and 55.8% (95% CI: 41.3%-69.5%) per RECIST version 1.1. The DCR was 100% by both criteria. The median DoR was 12.1 months per mRECIST and 10.5 months per RECIST version 1.1. With a median follow-up of 22.0 months (range: 1.6-57.3), the median PFS was 16.8 months (95% CI: 12.9-20.5) per mRECIST and 16.6 months (95% CI: 12.8-20.2) per RECIST version 1.1. The median OS was 24.9 months (95% CI: 21.7-35.6). Treatment-emergent adverse events (TEAEs) of any grade occurred in 45 patients (86.5%), with fatigue (30.8%) being the most common. Grade ≥3 TEAEs were observed in 17.3% of patients. Conclusion:First-line nivolumab plus lenvatinib and intra-arterial locoregional therapy showed encouraging antitumor activity and a manageable safety profile in unresectable HCC.
Purpose:Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. In middle-income settings, fragmentation of care may delay diagnosis and limit access to timely treatment. This study aimed to describe the sociodemographic and clinical characteristics, treatment patterns, and overall survival of patients with HCC managed at a Center of Clinical Excellence (CCE). Patients and Methods:We conducted a retrospective descriptive cohort study of adults (≥18 years) with HCC managed at a CCE between September 2022 and December 2025. Baseline variables included etiology, comorbidities, Child-Pugh class, Model for End-Stage Liver Disease (MELD) score, Barcelona Clinic Liver Cancer (BCLC) stage, and alpha-fetoprotein (AFP) levels. Treatment strategies and clinical course, including stage migration, liver transplantation, and death, were described. Overall survival was estimated using the Kaplan-Meier method. Results:A total of 134 patients were included. Median age was 67.93 years (IQR 63.12-72.59) and 61.19% were men. The most common underlying etiology was metabolic dysfunction-associated steatotic liver disease (MASLD) (34.38%). Most patients were diagnosed at early BCLC stages 0/A (64.18%; n = 86). Ablation and transarterial chemoembolization were the most frequently used treatments, and liver transplantation was performed in 9.70% of patients. After a median follow-up of 21 months, median overall survival was not reached; estimated survival was 93.8% at 1 year and 80.0% at 3 years. Conclusion:In this retrospective cohort managed at a CCE, MASLD was the most frequent underlying etiology, and patients were diagnosed at early stages BCLC stages 0/A. Treatment patterns were dominated by locoregional therapies, and median overall survival was not reached during the available follow-up period. These findings provide real-world data on HCC care in a middle-income setting and highlight the clinical relevance of describing treatment trajectories and survival within structured multidisciplinary care programs.
Balloon-occluded transarterial chemoembolization (B-TACE) uses temporary microballoon occlusion to reduce distal arterial pressure and promote dense, selective deposition of chemoembolic material within the tumor and its drainage territory. Observational comparative studies and a meta-analysis suggest higher complete response and objective response rates than conventional TACE (C-TACE), especially in 3-5 cm tumors. However, randomized evidence and a proven survival advantage are lacking. Clinical benefit is therefore most plausible in carefully selected patients with preserved liver function, a limited tumor burden amenable to segmental treatment, and anatomy in which collateral inflow does not prevent a meaningful pressure reduction. Measurement of balloon-occluded arterial stump pressure may help characterize hemodynamics, but the proposed <64 mmHg threshold is not universally reproducible or routinely available. B-TACE has a broadly comparable overall safety profile to C-TACE, while non-target or excessive peripheral embolization can injure the peribiliary plexus and cause biloma or hepatic abscess. Future priorities include standardized technical endpoints, prospective randomized comparisons, validated selection criteria, imaging-based hemodynamic prediction, and rigorously designed combinations with systemic or other locoregional therapies.
Purpose:Dynamic changes in circulating biomarkers may reflect tumor biology and host responses more accurately than static measurements. This study aimed to develop and internally validate a dynamic prognostic model for progression-free survival (PFS) and overall survival (OS) in patients with hepatocellular carcinoma (HCC) by integrating longitudinal biomarker trajectories with clinical variables. Patients and Methods:We retrospectively analyzed 379 patients with HCC treated at a single center in China. Latent class mixed models were used to identify circulating biomarker trajectories, which were integrated with clinical variables to construct the Integrated Multi-Biomarker Trajectory (IMBT) model. The model was compared with BCLC stage, a baseline biomarker model, and an AFP trajectory model. Discrimination, calibration, and clinical utility were assessed using C-indices and time-dependent AUCs, calibration plots, calibration slopes and Brier scores, and decision curve analysis (DCA), respectively. Internal subgroup validation was performed in a treatment-defined subset of 327 patients from the same center and source cohort who received PD-(L)1 inhibitor plus molecular targeted therapy. A predefined AFP-negative subgroup analysis was performed using baseline/cycle-0 AFP <20 ng/mL, which was used only to define the subgroup. Results:AFP, D-dimer, and absolute lymphocyte count (ALC) trajectories independently predicted PFS and OS. Sharp-falling AFP trajectories were associated with favorable outcomes, whereas persistently high or rising AFP and D-dimer trajectories and lower ALC trajectories indicated poorer prognosis. The IMBT model achieved C-indices of 0.741 for PFS and 0.728 for OS. For PFS, the C-index exceeded those of the BCLC, baseline biomarker, and AFP trajectory models by 0.108, 0.124, and 0.039, respectively. The corresponding C-indices were 0.730 and 0.724 in the internal PD-(L)1 plus MTT subgroup. Calibration slopes at 12 and 24 months were 1.176 and 1.509 for PFS and 0.898 and 1.014 for OS, respectively, while DCA demonstrated positive net benefit across clinically relevant thresholds. In AFP-negative patients, the PFS/OS C-indices were 0.647/0.634 in the full cohort and 0.692/0.683 in the PD-(L)1 plus MTT subgroup. Conclusion:Longitudinal trajectories of AFP, D-dimer, and ALC provide independent and complementary prognostic information. By integrating dynamic biomarker patterns with clinical features, the IMBT model improved risk stratification compared with conventional staging, baseline biomarker, and AFP-only trajectory models. These findings support further prospective external validation of the model for dynamic prognostic assessment and risk-adapted monitoring in HCC.
Background:Curative hepatectomy is the treatment of choice for resectable hepatocellular carcinoma (HCC). For recurrence or progression beyond locoregional therapy (LRT), multikinase inhibitors (MKIs) remain established first-line options. However, whether prior curative resection is associated with a survival benefit after MKI initiation remains unclear. We employed inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to compare survival in MKI-treated patients with and without prior hepatectomy. Methods:This retrospective cohort study enrolled 203 patients with unresectable HCC receiving first-line sorafenib or lenvatinib at a single Taiwanese referral hospital (2018-2023). Patients were classified into recurrent HCC (rHCC, n = 58; with prior curative resection) and primary unresectable HCC (uHCC, n = 145; without prior resection) groups. Overall survival (OS) and progression-free survival (PFS) were evaluated using stabilized IPTW with multivariable Cox regression, and PSM as a sensitivity analysis. Results:Over a 13.2-month median follow-up, median OS was longer in the rHCC group (27.0 vs 11.8 months; P = 0.027). After IPTW adjustment, prior resection was independently associated with longer OS (HR: 0.54; 95% CI: 0.36-0.81; P = 0.003) and PFS (HR: 0.61; 95% CI: 0.42-0.89; P = 0.010). PSM yielded concordant results (OS HR: 0.42; 95% CI: 0.26-0.70; P < 0.001; PFS HR: 0.55; 95% CI: 0.35-0.86; P = 0.010). This survival advantage was primarily observed in patients with late recurrence (≥24 months from hepatectomy). High tumor burden was an independent adverse prognostic factor for OS (HR: 1.58; 95% CI: 1.08-2.30; P = 0.017). Conclusion:In patients receiving first-line MKIs, prior curative resection was associated with longer OS and PFS. The better liver reserve and more favorable tumor biology that made these patients suitable candidates for surgery may persist into the systemic therapy phase. Therefore, future clinical trials might consider prespecifying prior resection as a stratification factor.
Objective:Hepatocellular carcinoma (HCC) has poor prognosis and variable immunotherapy response. Resveratrol exhibits anti-HCC activity, but its direct targets and association with immunotherapy response are unclear. This study identifies core resveratrol targets in HCC and evaluates their prognostic and predictive value. Methods:Resveratrol targets were intersected with TCGA-LIHC differentially expressed genes. A prognostic risk model was built using LASSO-Cox regression. Drug-target binding was assessed by molecular dynamics simulations and qRT-PCR. Single-cell and spatial transcriptomics, cell-cell communication, and a pan-immunotherapy cohort were used to investigate KIF11. An HCC mouse model validated immunomodulatory effects via flow cytometry. Results:Thirty-four resveratrol-associated targets were identified, enriched in metabolism pathways. A nine-gene risk model showed robust prognostic performance. Resveratrol stably binds to KIF11's ATP-binding pocket. KIF11 is overexpressed in malignant hepatocytes and proliferating T cells; KIF11⁺ cells orchestrate VEGF-mediated microenvironment remodeling. High KIF11 expression correlated with poor prognosis but predicted superior survival in the immunotherapy cohort, a phenomenon attributed to the observation that KIF11-high tumors exhibit both enhanced immunogenicity and active immunosuppression. In vivo, resveratrol enhanced CD8⁺ T cell infiltration, proliferation, effector function, and central memory T cells, while reducing Tregs. Conclusion:KIF11 drives HCC progression and predicts immunotherapy response. It is a candidate direct resveratrol target and a potential biomarker for patient stratification in immune checkpoint therapy, although further experimental validation is warranted.
Weifu Liu,1,* Bohua Yu,2,* Fuqun Wei,3,4,* Songhui Wu,5,* Jian He,6 Peishu Huang,7 Xiang You,3,4 Zhisheng Chen,3,4 Ziqi Lin,3,4 Shaowu Zhuang,5 Zhongwu Chen,3,4 Yiping Chen3,41Department of Oncology and Vascular Interventional Therapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, People’s Republic of China; 2Department of Hepatobiliary Surgery, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, 353000, People’s Republic of China; 3Department of Interventional Radiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 4Department of Interventional Radiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, People’s Republic of China; 5Department of Interventional Radiology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People’s Republic of China; 6Department of Interventional Radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 7Department of Radiology, Jinjiang Municipal Hospital (Shanghai Sixth People’s Hospital Fujian Campus), Jinjiang, 362200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongwu Chen, Email 708920855@qq.com Yiping Chen, Email ptchenyp@163.comBackground: Prognostic stratification remains suboptimal in unresectable hepatocellular carcinoma (uHCC) treated with locoregional therapy (LRT) plus lenvatinib and PD-1 blockade. Existing staging systems insufficiently reflect host nutritional–immune status.Methods: We included a multicenter retrospective study including 347 patients with uHCC treated with LRT, lenvatinib, and a PD-1 inhibitor. Nine prognostic models were developed using Cox regression Model performance was evaluated using time-dependent AUC (tdAUC), calibration, and decision curve analysis (DCA). A nomogram was constructed for individualized survival prediction.Results: Median overall survival (OS) was 33.1 months (95% CI, 30.5-not reached) and median progression-free survival (PFS) was 10.2 months (95% CI, 9.0– 12.6) in the overall cohort. The integrated model (incorporating tumor burden, ALBI grade, AFP, PNI) showed superior discrimination, with C-indices of 0.780 (training cohort) and 0.785 (validation cohort). The tdAUCs for OS and PFS were 0.892 and 0.807, respectively, in the training cohort and 0.861 and 0.819, respectively, in the validation cohort. Calibration plots demonstrated good agreement between predicted and observed 2-year OS in both cohorts. Risk stratification based on tertiles yielded significantly separated survival curves in both cohorts (all P< 0.001). The nomogram achieved strong predictive accuracy, with 1-, 2-, and 3-year AUCs of 0.879, 0.808, and 0.787, respectively.Conclusion: PNI-integrated prognostic model provides robust risk stratification for uHCC patients receiving LRT combined with lenvatinib and PD-1 inhibitors, supporting individualized pre-treatment risk assessment.Keywords: hepatocellular carcinoma, prognostic nutritional index, lenvatinib, PD-1 inhibitor, locoregional therapy, nomogram
Jia-Min Wu,1 Guan-Hua Li,2 Cheng-Chun Lee,3 Jie-Ying Chen,4 Shun-Fa Yang,5,6 Kuan-Chun Hsueh7,81Department of Applied Statistics, National Taichung University of Science and Technology, Taichung, Taiwan; 2Division of Gastroenterology and Hepatology Medicine, Department of Internal Medicine, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan; 3Division of Diagnostic Radiology, Department of Medical Imaging, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan; 4Department of Medical Research, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan; 5Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 6Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; 7Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 8Division of General Surgery, Department of Surgery, Tungs’ Taichung MetroHarbor Hospital, Taichung, TaiwanCorrespondence: Kuan-Chun Hsueh, Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, 145 Xingda Road, South Dist, Taichung City, 402202, Taiwan, Tel +886 930897638, Email sandersyeh@yahoo.com.twBackground: Curative hepatectomy is the treatment of choice for resectable hepatocellular carcinoma (HCC). For recurrence or progression beyond locoregional therapy (LRT), multikinase inhibitors (MKIs) remain established first-line options. However, whether prior curative resection is associated with a survival benefit after MKI initiation remains unclear. We employed inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to compare survival in MKI-treated patients with and without prior hepatectomy.Methods: This retrospective cohort study enrolled 203 patients with unresectable HCC receiving first-line sorafenib or lenvatinib at a single Taiwanese referral hospital (2018– 2023). Patients were classified into recurrent HCC (rHCC, n = 58; with prior curative resection) and primary unresectable HCC (uHCC, n = 145; without prior resection) groups. Overall survival (OS) and progression-free survival (PFS) were evaluated using stabilized IPTW with multivariable Cox regression, and PSM as a sensitivity analysis.Results: Over a 13.2-month median follow-up, median OS was longer in the rHCC group (27.0 vs 11.8 months; P = 0.027). After IPTW adjustment, prior resection was independently associated with longer OS (HR: 0.54; 95% CI: 0.36– 0.81; P = 0.003) and PFS (HR: 0.61; 95% CI: 0.42– 0.89; P = 0.010). PSM yielded concordant results (OS HR: 0.42; 95% CI: 0.26– 0.70; P < 0.001; PFS HR: 0.55; 95% CI: 0.35– 0.86; P = 0.010). This survival advantage was primarily observed in patients with late recurrence (≥ 24 months from hepatectomy). High tumor burden was an independent adverse prognostic factor for OS (HR: 1.58; 95% CI: 1.08– 2.30; P = 0.017).Conclusion: In patients receiving first-line MKIs, prior curative resection was associated with longer OS and PFS. The better liver reserve and more favorable tumor biology that made these patients suitable candidates for surgery may persist into the systemic therapy phase. Therefore, future clinical trials might consider prespecifying prior resection as a stratification factor.Keywords: hepatocellular carcinoma, post-hepatectomy recurrence, multikinase inhibitor, propensity score, inverse probability of treatment weighting, surgical selection effect
Xiaoli Jia, Yuanyi Chen, Xiaomeng Cui, Yan Tian, Dandan Feng, Wenjun WangDepartment of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Wenjun Wang, Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email wenjun_wang@xjtu.edu.cnAbstract: Balloon-occluded transarterial chemoembolization (B-TACE) uses temporary microballoon occlusion to reduce distal arterial pressure and promote dense, selective deposition of chemoembolic material within the tumor and its drainage territory. Observational comparative studies and a meta-analysis suggest higher complete response and objective response rates than conventional TACE (C-TACE), especially in 3– 5 cm tumors. However, randomized evidence and a proven survival advantage are lacking. Clinical benefit is therefore most plausible in carefully selected patients with preserved liver function, a limited tumor burden amenable to segmental treatment, and anatomy in which collateral inflow does not prevent a meaningful pressure reduction. Measurement of balloon-occluded arterial stump pressure may help characterize hemodynamics, but the proposed < 64 mmHg threshold is not universally reproducible or routinely available. B-TACE has a broadly comparable overall safety profile to C-TACE, while non-target or excessive peripheral embolization can injure the peribiliary plexus and cause biloma or hepatic abscess. Future priorities include standardized technical endpoints, prospective randomized comparisons, validated selection criteria, imaging-based hemodynamic prediction, and rigorously designed combinations with systemic or other locoregional therapies.Keywords: balloon-occluded transarterial chemoembolization, transarterial chemoembolization, hepatocellular carcinoma
Cineng Xu,1,* Yun Yang,1,* Dongmei Gou,1 Xiafei Wei,1 Qichao Yu,1 Jianguo Huang,1 Qingxian Cai,1 Hongzhong Zhou,2 Yong Xu11Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 2Department of Laboratory Medicine, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Medical Innovation Technology Transformation Center of Shenzhen Second People’s Hospital, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Xu, Institute for Hepatology, Shenzhen Third People’s Hospital, No. 29 Bulan Road, Longgang District, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-61222333, Fax +86-755-61238928, Email xuyong_2024@163.com Hongzhong Zhou, Department of Laboratory Medicine, Shenzhen Second People’s Hospital, No. 3002 Sungang West Road, Futian District, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-83366388, Fax +86-755-83364277, Email zhouhongzhong888@163.comPurpose: Dynamic changes in circulating biomarkers may reflect tumor biology and host responses more accurately than static measurements. This study aimed to develop and internally validate a dynamic prognostic model for progression-free survival (PFS) and overall survival (OS) in patients with hepatocellular carcinoma (HCC) by integrating longitudinal biomarker trajectories with clinical variables.Patients and Methods: We retrospectively analyzed 379 patients with HCC treated at a single center in China. Latent class mixed models were used to identify circulating biomarker trajectories, which were integrated with clinical variables to construct the Integrated Multi-Biomarker Trajectory (IMBT) model. The model was compared with BCLC stage, a baseline biomarker model, and an AFP trajectory model. Discrimination, calibration, and clinical utility were assessed using C-indices and time-dependent AUCs, calibration plots, calibration slopes and Brier scores, and decision curve analysis (DCA), respectively. Internal subgroup validation was performed in a treatment-defined subset of 327 patients from the same center and source cohort who received PD-(L)1 inhibitor plus molecular targeted therapy. A predefined AFP-negative subgroup analysis was performed using baseline/cycle-0 AFP < 20 ng/mL, which was used only to define the subgroup.Results: AFP, D-dimer, and absolute lymphocyte count (ALC) trajectories independently predicted PFS and OS. Sharp-falling AFP trajectories were associated with favorable outcomes, whereas persistently high or rising AFP and D-dimer trajectories and lower ALC trajectories indicated poorer prognosis. The IMBT model achieved C-indices of 0.741 for PFS and 0.728 for OS. For PFS, the C-index exceeded those of the BCLC, baseline biomarker, and AFP trajectory models by 0.108, 0.124, and 0.039, respectively. The corresponding C-indices were 0.730 and 0.724 in the internal PD-(L)1 plus MTT subgroup. Calibration slopes at 12 and 24 months were 1.176 and 1.509 for PFS and 0.898 and 1.014 for OS, respectively, while DCA demonstrated positive net benefit across clinically relevant thresholds. In AFP-negative patients, the PFS/OS C-indices were 0.647/0.634 in the full cohort and 0.692/0.683 in the PD-(L)1 plus MTT subgroup.Conclusion: Longitudinal trajectories of AFP, D-dimer, and ALC provide independent and complementary prognostic information. By integrating dynamic biomarker patterns with clinical features, the IMBT model improved risk stratification compared with conventional staging, baseline biomarker, and AFP-only trajectory models. These findings support further prospective external validation of the model for dynamic prognostic assessment and risk-adapted monitoring in HCC.Keywords: hepatocellular carcinoma, alpha-fetoprotein, D-dimer, absolute lymphocyte count, progression-free survival, overall survival
Hepatocellular carcinoma (HCC) is a highly malignant cancer closely related to the chronic inflammation induced by persistent liver damage. Various risk factors, including chronic hepatitis B/C virus infections, alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease, aflatoxins exposure, and metabolic disorders, contribute to genetic mutations in hepatocytes, leading to sustained cellular damage and apoptosis. These processes foster a chronic inflammatory microenvironment that activates hepatic stellate cells, promotes extracellular matrix deposition, and triggers aberrant regenerative repair, ultimately advancing liver fibrosis, cirrhosis, and HCC. The transition from chronic liver injury to HCC is governed by two interconnected mechanistic layers: initiating triggers-viral infection and hepatocyte death-that provide the substrate for malignant transformation, and modulatory systems that determine the trajectory of this process. Recent studies have revealed that diverse cell types and molecular signaling pathways form an intercellular regulatory network that fosters an inflammatory and carcinogenic microenvironment. This review focuses on three such modulatory systems-the hepatic immune microenvironment, the gut-liver axis, and neuroregulation-and examines how their interplay influences malignant behaviors including cell transformation, proliferation, and apoptosis. We systematically overview the key cellular constituents, fundamental molecular mechanisms, and core signaling pathways governing inflammation-induced hepatocarcinogenesis, and discuss potential therapeutic targets emerging from current research. A deeper understanding of these fundamental pathological mechanisms provides a conceptual framework for elucidating the initiation and progression of HCC. It also offers a theoretical basis for the future development of preventive and targeted therapeutic strategies, although the translation of these mechanistic insights into clinically effective interventions-particularly for cancer prevention-will require rigorous validation in large-scale, prospective human studies.
Background:Belonging to the RNA-binding protein family, Pumilio RNA binding family member 1 (PUM1) modulates gene expression post-transcriptionally through the recognition of particular motifs within the 3' untranslated region of its target transcripts. The present investigation seeks to elucidate PUM1's contribution to HCC pathogenesis and advancement, while also probing the molecular mechanisms that underpin its function. Methods:Publicly available datasets were employed to examine PUM1 transcript abundance in hepatocellular carcinoma, along with its relationship to clinicopathological parameters and prognostic outcomes. PUM1 protein levels were subsequently corroborated in clinical HCC specimens via immunoblotting and immunohistochemical staining. To explore the biological functions of PUM1, we established HCCLM3 cell lines with PUM1 overexpression and knockdown. We then evaluated proliferation via EdU, colony formation, and CCK‑8 assays; apoptosis via TUNEL and flow cytometry; mitochondrial membrane integrity and calcium balance using JC‑1, Mito‑Tracker, and Rhod‑2; and oxygen species (ROS) accumulation via MitoSOX and DCFH‑DA. The downstream molecular pathways were further examined by Western blotting. Results:HCC tissues exhibit markedly upregulated PUM1 levels, a feature tightly correlated with poor prognosis. In vitro, PUM1 preserved mitochondrial membrane integrity and calcium homeostasis in HCC cells, while suppressing the accumulation of reactive oxygen species (ROS). Additionally, PUM1 inhibited programmed cell death and promoted cell proliferation. These biological activities were closely associated with the PI3K-AKT signaling pathway. Conversely, knockdown of PUM1 significantly impaired HCC cell proliferation and induced apoptosis. Conclusion:PUM1 promotes HCC cell proliferation and suppresses mitochondria‑mediated apoptosis, effects that are closely associated with activation of the PI3K-AKT pathway.
