Journal of Hepatocellular Carcinoma最新文献

Purpose: The prognosis of hepatocellular carcinoma (HCC) with extrahepatic metastases (EM) is poor. The efficacy and safety of transcatheter arterial chemoembolization combined with lenvatinib plus anti-programmed cell death 1 inhibitors (triple therapy) for HCC with EM remains unclear. In this study, we aimed to determine the efficacy and safety of triple therapy in HCC patients with EM.

Patients and methods: This study retrospectively reviewed HCC patients with EM who received triple therapy and analyzed their survival rate using the Kaplan-Meier method. Univariate prognostic analysis of each data point was performed using the Log rank test, and multivariate prognostic analysis was performed using the Cox proportional risk regression model.

Results: Among 60 HCC patients with EM who underwent triple therapy, the most common sites of metastasis were as follows (in descending order): the lungs (n=27), lymph nodes (n=22), and bones (n=10). After triple therapy, the median progression-free survival and median overall survival were 6 and 18.63 months, respectively. The 6-month, 1-year, and 2-year cumulative survival rates were 87.7%, 68.6%, and 26.8%, respectively. In the multivariate analysis, neutrophil-to-lymphocyte ratio (NLR) ≥4 and alpha-fetoprotein (AFP) level ≥400 ng/mL were independently associated with overall survival.

Conclusion: Our findings revealed that triple therapy is an effective, well-tolerated regimen for HCC patients with EM. AFP level and NLR are prognostic risk factors for triple therapy in this patient population.

Purpose: The response to transarterial chemoembolization (TACE) varies among individuals with hepatocellular carcinoma (HCC). This study aimed to identify a biomarker for predicting TACE response in HCC patients and to investigate its correlations with the tumor microenvironment and pre-TACE radiomics features.

Patients and methods: GSE104580 data were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed gene analysis and machine learning algorithms were used to identify genes for constructing the TACE failure signature (TFS). TFS scores were then calculated for HCC patients in The Cancer Genome Atlas (TCGA) cohort. After obtaining images from The Cancer Imaging Archive (TCIA), tumor labeling and radiomics feature extraction, the Rad-score model was generated. Correlation analysis was performed between the TFS score and the Rad-score. CIBERSORT, ssGSEA and TME analysis were performed to explore differences in the immune landscape among distinct risk groups. The immunotherapy response was compared between different groups.

Results: ADH1C, CXCL11, EMCN, SPARCL1 and LIN28B were selected and incorporated into the TFS, which demonstrated satisfactory performance in predicting TACE response. Patients in the high TFS score group had poorer overall survival (OS) than those in the low TFS score group. The Rad-score model was constructed using six radiomics features, and the Rad-score was significantly correlated with hub gene expression and the TFS score. The high-TFS group was also characterized by an immunosuppressive tumor microenvironment and exhibited unfavorable responses to immunotherapy with PD-1 and CTLA-4 checkpoint inhibitors.

Conclusion: This study established a transcriptomic biomarker for predicting the efficacy of TACE that correlates with radiomics features on pretreatment imaging, tumor immune microenvironment characteristics, and the efficacy of immunotherapy and targeted therapy in HCC patients.

Purpose: Yiqi Liangxue Jiedu prescription (YLJP), a Chinese medicine that is commonly used to prevent liver cancer and is authorized by a national patent (patent No. ZL202110889980.5) has a therapeutic effect on precancerous lesions; however, the underlying mechanism remains unclear. This study is aimed at determining the clinical therapeutic efficacy of YLJP in patients with precancerous liver lesions and to explore and validate its possible effector mechanism.

Patients and methods: The 1-year incidence of hepatocellular carcinoma (HCC) was retrospectively analyzed in 241 patients with cirrhosis complicated by abnormal alpha-fetoprotein precancer. Network pharmacological analysis, molecular docking, and molecular dynamics simulation were used to explore the key targets and compounds of YLJP in treating HCC. Immunohistochemical methods were used to detect the expression of key proteins in tumor and cirrhotic tissues. Finally, the mechanism underlying the effects of YLJP was verified in rats with precancerous lesions.

Results: The 1-year incidence of HCC was lower in the YLJP group than in the Western medicine group. The Wnt pathway protein, CTNNB1, is a key target of YLJP in preventing and treating HCC, and the canonical Wnt pathway is the key signaling pathway and is overexpressed in human liver tumors. In vivo experiments showed that YLJP significantly inhibited the canonical Wnt pathway and reduced the abnormal differentiation of hepatic oval cells. The binding of CTNNB1 to oleanolic acid, stigmasterol, and beta-sitosterol was found to be stable, indicating the action of these compounds in treating HCC.

Conclusion: YLJP reduces the 1-year incidence of HCC, with its mechanism likely due to oleanolic acid, beta-sitosterol, and stigmasterol inhibition of the CTNNB1 activation of the β-catenin protein, which in turn regulates the Wnt signaling pathway and prevents the abnormal differentiation of hepatic oval cells into cancer cells, thus delaying the occurrence and progression of the disease.

Purpose: Diabetes mellitus (DM) negatively impacts chronic hepatitis B patients, but its role in those with HBV-related hepatocellular carcinoma (HCC) undergoing ablation remains unclear. This study aims to evaluate the influence of DM on recurrence patterns and overall survival (OS) among patients with HBV-related HCC undergoing ablation.

Patients and methods: We retrospectively enrolled 372 patients receiving thermal ablation for HBV-related HCC, including 96 (25.8%) patients with DM. Factors associated with local tumor progression (LTP), distant recurrence, and OS were analyzed. The prognostic value of DM in IMbrave050-defined high-risk population was validated.

Results: DM did not correlate with LTP, whereas patients with DM had significantly higher risk of distant recurrence (median time to recurrence 23.7 versus 46.2 months, p=0.032), poorer OS (median OS 75.6 versus 106 months, p=0.011), and poorer post-recurrence survival (70.7 versus 106 months, p=0.009). In multivariate analysis, DM (hazard ratio (HR)=1.466, p=0.012), FIB-4 score, multiple tumors, and AFP level were independent predictors of distant recurrence, while DM (HR=1.424, p=0.028), ALBI score, tumor size, AFP and creatinine levels were significantly associated with OS. A DM-based risk score effectively discriminated the risk of distant recurrence. The IMbrave050 criteria could stratify the risk of LTP but not distant recurrence. DM status further discriminated the risk of distant recurrence and mortality in the IMbrave050-defined high-risk population.

Conclusion: Patients with DM had an increased risk of distant recurrence and mortality after thermal ablation for HBV-related HCC, highlighting the importance of increasing awareness of DM and implementing rigorous post-ablation monitoring for diabetic HCC patients.

Background: Hepatocellular carcinoma (HCC) with pulmonary metastasis (PM) significantly worsens prognosis, and current treatment options remain limited.

Methods: A retrospective study was conducted on HCC patients treated with sintilimab combined with lenvatinib at three hospitals in China between 2020 and 2021. Progression-free survival (PFS), overall survival (OS), and tumor response based on RECIST 1.1 were compared. Treatment safety was assessed by analyzing treatment-related adverse events (TRAEs).

Results: Among 144 patients, 105 received sintilimab combined with lenvatinib (S+L), while 39 were treated with radiotherapy combined with sintilimab and lenvatinib (RT+S+L). The RT+S+L group showed superior outcomes in OS (25 months vs 16 months, HR = 0.58, 95% CI = 0.35-0.94, P=0.025) and PFS (14 months vs 6 months, HR = 0.61, 95% CI = 0.40-0.94, P=0.022) compared to the S+L group. Similarly, the RT+S+L group exhibited significantly higher objective response rate (ORR) and disease control rate (DCR) compared to the S+L group (61.5% vs 27.6%, P<0.001; 94.9% vs 76.2%, P=0.011). The most common grade 3/4 TRAEs in the RT+S+L group were hypertension, decreased platelet count, elevated total bilirubin, and proteinuria.

Conclusion: Radiotherapy combined with sintilimab and lenvatinib is an effective strategy for treating HCC with pulmonary metastasis. These findings highlight the critical role of radiotherapy in the management of HCC.

Background: Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the microenvironment of hepatocellular carcinoma (HCC). However, the mechanisms through which CAFs influence the progression of HCC remain incompletely understood.

Methods: Single-cell RNA sequencing datasets (GSE158723 and GSE112271) were retrieved from the Gene Expression Omnibus (GEO) database at the National Center for Biotechnology Information (NCBI) and analyzed using R software. Our analysis suggested that CAFs may promote liver cancer cell development, possibly through the interaction of pleiotrophin (PTN) and syndecan-2 (SDC2). Clinical samples from HCC patients were collected and processed into frozen sections and single-cell suspensions for Masson staining, immunofluorescence staining, and flow cytometry. Additionally, Huh7 liver cancer cells and LO2 normal liver cells were cultured and subjected to immunofluorescence assays using cell slides.

Results: The proportion of CAFs in cancerous tissues was higher than in adjacent non-cancerous tissues, and pleiotrophin (PTN) expression was elevated in cancer tissues compared to adjacent tissues. These findings aligned with the results of the single-cell RNA sequencing (scRNA-seq) analysis. Furthermore, SDC2 expression was significantly upregulated in Huh7 liver cancer cells compared to LO2 normal liver cells.

Discussion: This study suggests that CAFs may contribute to HCC progression via the PTN/SDC2 signaling pathway. Our findings provide deeper insights into the interactions between CAFs and HCC cells within the tumor microenvironment (TME).

Hepatocellular carcinoma is the fifth leading cancer in related diseases most commonly in men and women. The curative treatments of liver cancer are short-listed, associated with toxicities and therapeutically. Emerging nanotechnologies exhibited the possibility to treat or target liver cancer. Over the years, to phytosome solid lipid nanoparticles, gold, silver, liposomes, and phospholipid nanoparticles have been produced for liver cancer therapy, and some evidence of their effectiveness has been established. Ideas are limited to the laboratory scale, and in order to develop active targeting of nanomedicine for the clinical aspects, they must be extended to a larger scale. Thus, the current review focuses on previously and presently published research on the creation of phytosomal nanocarriers for the treatment of hepatocellular carcinoma. In hepatocellular carcinoma (HCC), phytosomal nanotherapeutics improve the targeted delivery and bioavailability of phytochemicals to tumor cells, thereby reducing systemic toxicity and increasing therapeutic efficacy. In order to address the intricate molecular processes implicated in HCC, this strategy is essential.

Purpose: To construct a 2.5-dimensional (2.5D) CT radiomics-based deep learning (DL) model to predict early postoperative recurrence of hepatocellular carcinoma (HCC).

Patients and methods: We retrospectively analyzed the data of patients who underwent HCC resection at 2 centers. The 232 patients from center 1 were randomly divided into the training (162 patients) and internal validation cohorts (70 patients); 91 patients from center 2 formed the external validation cohort. We developed a 2.5D DL model based on a central 2D image with the maximum tumor cross-section and adjacent slices. Multiple views (transverse, sagittal, and coronal) and phases (arterial, plain, and portal) were incorporated. Multi-instance learning techniques were applied to the extracted data; the resulting comprehensive feature set was modeled using Logistic Regression, RandomForest, ExtraTrees, XGBoost, and LightGBM, with 5-fold cross validation and hyperparameter optimization with Grid-search. Receiver operating characteristic curves, calibration curves, DeLong test, and decision curve analysis were used to evaluate model performance.

Results: The 2.5D DL model performed well in the training (AUC: 0.920), internal validation (AUC: 0.825), and external validation cohorts (AUC: 0.795). The 3D DL model performed well in the training cohort and poorly in the internal and external validation cohorts (AUCs: 0.751, 0.666, and 0.567, respectively), indicating overfitting. The combined model (2.5D DL+clinical) performed well in all cohorts (AUCs: 0.921, 0.835, 0.804). The Hosmer-Lemeshow test, DeLong test, and decision curve analysis confirmed the superiority of the combined model over the other signatures.

Conclusion: The combined model integrating 2.5D DL and clinical features accurately predicts early postoperative HCC recurrence.

Purpose: This study aims to explore the value of radiomics combined with clinical parameters in predicting recurrence-free survival (RFS) after the resection of hepatocellular carcinoma (HCC).

Patients and methods: In this retrospective study, a total of 322 patients with HCC who underwent contrast-enhanced computed tomography (CT) and radical surgical resection were enrolled and randomly divided into a training group (n = 223) and a validation group (n = 97). In the training group, Univariate and multivariate Cox regression analyses were employed to obtain clinical variables related to RFS for constructing the clinical model. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were employed to construct the radiomics model, and the clinical-radiomics model was further constructed. Model prediction performance was subsequently assessed by the area under the time-dependent receiver operating characteristic curve (AUC) and calibration curve. Additionally, Kaplan-Meier analysis was used to evaluate the model's value in predicting RFS. Correlations between radiomics features and pathological parameters were analyzed.

Results: The clinical-radiomics model predicted RFS at 1, 2, and 3 years more accurately than the clinical or radiomics model alone (training group, AUC = 0.834, 0.765 and 0.831, respectively; validation group, AUC = 0.715, 0.710 and 0.793, respectively). The predicted high-risk subgroup based on the clinical-radiomics nomogram had shorter RFS than predicted low-risk subgroup in data sets, enabling risk stratification of various clinical subgroups. Correlation analysis revealed that the rad-score was positively related to microvascular invasion (MVI) and Edmondson-Steiner grade.

Conclusion: The clinical-radiomics model effectively predicts RFS in HCC patients and identifies high-risk individuals for recurrence.

Purpose: Radiofrequency ablation (RFA) is a micro-invasive treatment for early-stage HCC patients. Stereotactic body radiation therapy (SBRT) has also been proven an effective and safe treatment for HCC patients. This multi-center study is to compare the efficacy of computed tomography (CT)-guided RFA and CT-based SBRT in naïve HCC patients with tumor diameters ≤5 cm.

Patients and methods: This retrospective cohort study included 1001 treatment-naïve HCC patients from three hospitals or medical centers. The patients received RFA (n = 481) or SBRT (n = 520) treatment between December 2011 and May 2019. Furthermore, subgroup analyses of all patients were conducted based on Couinaud's classification of liver segments.

Results: After matching, the local control (LC) rates of the SBRT group were better than those of the RFA group (p=0.024*), which mainly referred to the patients whose tumors were located in the S7/S8 (p=0.006*). Among patients with tumors located in S1, nineteen patients (19/21) underwent SBRT. The 1-, 3- and 5-year LC rates were 100%, 87.8% and 87.8% in the SBRT group, and the 1-, 3- and 5-year OS rates were 100%, 69.8% and 69.8%, respectively. Moreover, the OS rates in S5/S6 group in RFA were higher than those in SBRT group.

Conclusion: The LC rates were better in the SBRT group than in the RFA group for the patients with lesions localized in S7/S8, and SBRT could also be a therapeutic option for patients with lesions in S1. Moreover, patients with tumors located in S5/S6 were better candidates for RFA treatment than SBRT.