Journal of Hepatocellular Carcinoma最新文献

Purpose: Let-7, a family of microRNA (miRNA) that regulates the timing of cell division, is associated with tumorigenesis and tumor progression. The factors that regulate let-7 and affect the prognosis of hepatocellular carcinoma (HCC) warrant further investigation.

Patients and methods: In this study, we first utilized the data from The Cancer Genome Atlas (TCGA) and employed bioinformatics methods to analyze the expression and function of let-7 in HCC. Subsequently, we retrieved the long non-coding RNAs (lncRNAs) that regulate let-7 from the StarBase database. Finally, through bioinformatics analysis of the TCGA-LIHC data and validation with clinical samples, we explored the relationship between let-7 and its related lncRNAs and clinical indicators such as HCC recurrence and survival.

Results: Let-7c was significantly downregulated in HCC, regulating tumor progression via pathways like PI3K-Akt and tumor-related miRNAs. LncRNAs SNHG16 negatively regulated let-7c expression in HCC (r = -0.160, p = 0.002). Both bioinformatics analysis and clinical sample validation revealed that high SNHG16 expression in HCC tissues was associated with shorter disease-free survival (HR = 1.711, 95% CI: 1.144-2.559, p = 0.009), higher recurrence rates (p < 0.001), and shorter overall survival (HR = 1.837, 95% CI: 1.283-2.629, p = 0.001).

Conclusion: SNHG16 negatively regulates let-7c and serves as a prognostic biomarker for HCC recurrence and survival.

Background: Hepatocellular carcinoma (HCC) with microvascular invasion (MVI) is associated with high recurrence risk after curative resection. While adjuvant immune checkpoint inhibitors (ICIs) have shown potential in improving outcomes, there is no consensus on their optimal duration, and the comparative effectiveness versus transcatheter arterial chemoembolization (TACE) remains unclear.

Methods: We conducted a retrospective multicenter cohort study of 399 patients with microvascular invasion-positive hepatocellular carcinoma who underwent curative resection between 2017 and 2024. Patients receiving adjuvant ICIs or TACE were compared. Propensity score matching (PSM) was used to adjust baseline differences. The primary endpoint was recurrence-free survival (RFS); overall survival (OS) was assessed as a secondary endpoint. Subgroup analysis evaluated the impact of ICI treatment duration.

Results: Among 399 patients, 132 received TACE alone, and 129 received ICI-based therapy. Median RFS was significantly longer in the ICI group than in the TACE group (35 months vs 16 months; HR = 0.50, 95% CI: 0.34-0.72; p = 0.00015). After PSM, ICI remained associated with improved RFS (HR = 0.54, 95% CI: 0.36-0.82; p = 0.0042), while the OS difference was not statistically significant. In the ICI subgroup, treatment duration ≥12 months was associated with superior RFS (HR = 0.46, 95% CI: 0.21-0.99; p = 0.041).

Conclusion: Among patients with HCC and MVI following curative resection, adjuvant ICIs therapy provides a significant recurrence-free survival advantage over TACE. Treatment durations shorter than 12 months may be insufficient, supporting the benefit of prolonged therapy.

Background: Predicting the prognosis of patients with HCC is challenging.

Aim: To evaluate the Assessment for Retreatment with TACE (ART) score in predicting survival after TACE retreatment and the value of adding post-TACE thrombocytopenia in improving its accuracy (P-ART).

Methods: Barcelona Clinic Liver Cancer (BCLC) stages A and B patients underwent TACE retreatment, and records were reviewed. Radiologic tumor response (RTR) after the first TACE was considered a partial response, while the absence of response is a stable or progressive disease. The one year overall survival (OS) from the second TACE was determined.

Results: One hundred and sixty patients included 88.1% men, age 60.7±7.2 years, Child-Pugh class A&B cirrhosis (n=133 and 27, respectively), mostly hepatitis C (96.3%), with BCLC-A&B (n=74 and 86, respectively). RTR was present in 82 patients. Variables associated with poor OS: baseline lower serum albumin and platelet count, besides follow-up absent radiologic tumor response, an increase in AST >25%, an increase in Child-Pugh score, and a fall in platelet count fall ≥10,000/mL³ before TACE2. By multivariate analysis, ART score parameters and platelet count fall were independent predictors of poor survival. RTR absence had the higher risk of mortality by 3.12 times than responding tumors. ART score subgroups (≤1.5 and ≥2.5 points, 81 and 79 patients, respectively) had no significant relation to OS (22.3 vs 16.7 months; P=0.07). On modifying the ART score by adding 3 points for fallen platelet count ≥10,000/mL³ (ART-P score), 113 patients scored 0-5 and 47 scored ≥5.5 with a median OS of 22 vs 11.2 months, respectively (P=0.01).

Conclusion: ART score could not identify patients who will benefit from TACE retreatment in intermediate-stage HCC patients, and the addition of platelet count reduction (P-ART) could improve its prognostic ability.

Background and aims: Early alpha-fetoprotein (AFP) response has been reported to predict the treatment efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced hepatocellular carcinoma (HCC). We evaluated the predictive value of another HCC tumor marker, protein induced by vitamin K absence/antagonists-II (PIVKA-II).

Methods: We prospectively established a cohort of advanced HCC patients who received ICI treatment at two medical centers. Serum PIVKA-II levels were obtained before and within 4 weeks after treatment initiation. Any decline in serum PIVKA-II levels was defined as an early PIVKA-II response. Treatment response, overall survival (OS), and progression-free survival (PFS) were compared between patients with and without an early PIVKA-II response.

Results: In total, 67 patients were included; liver reserve was Child-Pugh class A in all patients and albumin-bilirubin grade 1 in 67.2% of the patients. An early PIVKA-II response, which was observed in 19 (28.4%) patients, was associated with a higher objective response rate (50.0% vs 16.4%, p = 0.002). Patients with an early PIVKA-II response had superior OS (median 34.3 vs 13.7 months, p = 0.015) and PFS (median 8.4 vs 4.0 months, p = 0.049) compared with those without a response. In multivariate analysis, an early PIVKA-II response remained an independent predictor for longer OS (p = 0.012) and PFS (p = 0.044). An early PIVKA-II response can complement an early AFP response in predicting prognosis.

Conclusion: An early PIVKA-II response is predictive of tumor response and superior survival outcomes in patients who received ICIs for advanced HCC.

Background: Inflammation drives tumor development, with neutrophil extracellular traps (NETs) promoting progression through metastasis, immune suppression, and microenvironment modulation. However, the role of NETs-related genes in hepatocellular carcinoma (HCC) immunity response is still unclear.

Methods: We integrated single-cell RNA sequencing (GSE202642, seven tumor samples and four normal liver samples) and The Cancer Genome Atlas (TCGA, n=312) transcriptomic data to identify NETs-related gene signatures. Weighted gene co-expression network analysis (WGCNA) identified NETs-correlated gene modules, and LASSO-COX regression selected prognostic genes for risk stratification. A nomogram was developed to predict survival, while functional, mutation, immune, and drug sensitivity analyses highlighted intergroup differences. EdU and CCK-8 cell proliferation assays confirmed the role of NETs-related genes in HCC cell proliferation.

Results: The analysis revealed significant differences in survival time between high- and low-NETs groups. GAS2L3 and RTN3 were identified and validated as independent prognostic factors. ROC and decision curve analysis (DCA) demonstrated that the nomogram model combining NETs risk scores with clinical parameters exhibited robust prognostic performance. The high-risk subgroup was enriched in glycosphingolipid biosynthesis pathways and showed higher mutati843on rates, especially in TP53, CTNNB1, and MUC16, along with overexpression of immunosuppressive genes (VTCN1, LAIR1). In vitro experiments confirmed that GAS2L3 knockdown inhibited HepG2 and Huh7 cell proliferation.

Conclusion: Integrated multi-omics analysis revealed NETs-associated prognostic signatures in HCC, with GAS2L3 identified as a key gene linking NETs to tumor progression and therapeutic potential.

Purpose: The predictors of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) and a sustained virologic response after direct-acting antiviral therapy are not well known.

Patients and methods: Between September 2012 and March 2022, this retrospective study enrolled 4426 consecutive patients from 4 hospitals in Taiwan. The patients were divided into derivation (n = 3178) and validation (n = 1248) groups.

Results: In the derivation group, age, diabetes mellitus, platelet, albumin, and alpha-fetoprotein at 12 weeks after antiviral therapy were independent predictors of hepatocellular carcinoma. We incorporated these predictors into a novel risk prediction model called the AAAPD-C score (age, albumin, alpha-fetoprotein level, platelet count, and diabetes mellitus status), with total risk scores ranging from 0 to 12. The AAAPD-C score had an area under the receiver operating characteristic curve of 0.867 for the validation group at the end of follow-up. The risk score accurately classified patients in both groups into those with low, medium, and high risks. Patients without advanced liver fibrosis with medium-high AAAPD-C risk scores (4-12) had an annual incidence of HCC >4 per 1000 person-years.

Conclusion: The AAAPD-C score can predict the risk of HCC in patients with chronic hepatitis C and a sustained virologic response after direct-acting antiviral therapy. The tool is accurate and inexpensive, and clinicians can use it to identify patients with chronic hepatitis C at risk of HCC following viral eradication.

Background: Hepatocellular carcinoma (HCC) is characterized by high incidence and mortality rates, with hypoxia and anoikis resistance playing crucial roles in its progression and metastasis. While long non-coding RNA (lncRNA) significantly influence tumor biology, their roles in hypoxia-anoikis-resistant HCC remain unclear.

Methods: This study utilized RNA-seq data and clinical information from the TCGA and GEO databases to analyze 154 hypoxia- and anoikis-related lncRNAs and identify differentially expressed candidates. Cluster analysis with Consensus Cluster Plus revealed links to clinical outcomes and genomic features. Tumor immune microenvironment and pathway enrichment were assessed using CIBERSORT and ssGSEA. A nine-gene risk model was developed via LASSO Cox regression and internally validated. Preliminary experimental assays suggested that the identified lncRNAs may influence apoptosis under hypoxia and anoikis conditions.

Results: HCC patients were classified into two molecular subtypes, C1 and C2, with distinct prognostic outcomes and clinical features. These subtypes showed distinct immune infiltration characteristics and differential immunotherapy response scores. A nine-lncRNA prognostic model effectively predicted overall survival (OS), with the high-risk group showing increased immunosuppressive elements, such as Tregs and inactivated M0 macrophages, suggesting limited immunotherapy efficacy. Chemotherapy sensitivity analysis revealed varying drug responses between risk groups, while hypoxia- and anoikis-related lncRNAs, including LINC01554, FIRRE, LINC01139, LINC01134 and NBAT1 were downregulated in this model.

Conclusion: Research has demonstrated that hypoxia- and anoikis-related lncRNAs serve as reliable biomarkers for predicting liver cancer prognosis and immunotherapy response, offering potential for developing novel therapeutic targets and strategies to enhance treatment outcomes and patient prognosis.

Background: Cytokeratin 19 (CK19) serves as a significant prognostic indicator for hepatocellular carcinoma (HCC). However, it is uncertain if CK19 expression influences the prognosis and effectiveness of treatment in patients undergoing targeted therapy and immunotherapy for unresectable HCC. This study aimed to evaluate the prognostic value of CK19 expression in this patient population.

Methods: Patients with unresectable HCC who received combined targeted therapy and immunotherapy between January 2021 and December 2023 were retrospectively analyzed in this study. CK19 expression in tumor biopsy samples from patients before treatments were identified using immunohistochemistry. Propensity score matching (PSM) was conducted in a 1:2 ratio to balance baseline features between the CK19-positive and CK19-negative groups. Survival outcomes were analyzed using the Kaplan-Meier method along with the Cox regression model. Treatment response was evaluated based on mRECIST criteria.

Results: A total of 247 patients were included, and 126 were selected after-PSM (43 CK19-positive, 83 CK19-negative), with balanced baseline characteristics. After PSM, the CK19-negative group had a markedly prolonged median OS compared to the CK19-positive group (42.2 months vs 15.6 months, p < 0.001), along with an extended median PFS (28.9 months vs 7.3 months, p < 0.001). The ORR was significantly higher in the CK19-negative group than in the CK19-positive group (59.0% vs 18.6%, p < 0.001), and the DCR was also superior (96.4% vs 79.1%, p = 0.005). Multivariate Cox analysis found CK19 expression as an independent factor predicting OS and PFS.

Conclusion: In patients with unresectable HCC undergoing targeted therapy and immunotherapy, CK19 expression correlated with poorer survival outcomes and diminished therapeutic response. CK19 may serve as a valuable biomarker for prognosis and treatment stratification in advanced HCC, and CK19 screening may be incorporated into clinical trial stratification and clinical decision-making.

Background: Immunotherapy combined with targeted therapy is a key approach for patients with unresectable hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic value of clinical and CT features in Camrelizumab plus Apatinib treatment for these patients.

Materials and methods: A retrospective study was conducted on unresectable HCC patients who received camrelizumab plus Apatinib treatment from June 2019 to August 2021. Clinical and contrast-enhanced CT features were analyzed. Logistic regression identified predictors of objective response, and Cox regression assessed prognostic factors for progression-free survival (PFS) and overall survival (OS). Nomograms were constructed based on independent predictors.

Results: Among 109 patients, the median OS was 20 months, median PFS was 9 months, and the ORR was 43.1%. Independent predictors of objective response included AFP ≥ 400 ng/mL (OR = 6.31), NLR ≥ 3.2 (OR = 3.72), tumor numbers ≥ 3 (OR = 3.93), and ΔAER < 15% (OR = 10.99), the AUC for objective response model was 0.874. Independent factors for PFS included AFP ≥ 400 ng/mL (HR = 2.04) and ΔAER < 15% (HR = 2.57), resulting in a model AUC of 0.859. Independent factors for OS were NLR ≥ 3.2 (HR = 2.07), Tumor numbers ≥ 3 (HR = 2.68), and extrahepatic metastasis (HR = 2.32), with an AUC of 0.848 and 0.866 for 1- and 2-year survival, respectively.

Conclusion: Clinical and contrast-enhanced show significant prognostic value in patients receiving Camrelizumab plus Apatinib. The developed models may assist in identifying responsive patients and personalizing treatment strategies.

Purpose: This research constructs a prognostic model for overall survival (OS) in hepatocellular carcinoma (HCC) patients using radiomic features from non-contrast CT scans obtained within 24 hours after transarterial chemoembolization (TACE).

Patients and methods: Patients were retrospectively enrolled from three institutions to form training (n = 112) and validation (n = 56) cohorts from January 2016 to December 2023. All patients underwent a minimum of three TACE treatment sessions. January 2019 served as the cutoff point for dividing the dataset into training and validation cohorts. Univariate and multivariate Cox regression analyses were employed to obtain clinical variables related to OS 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 from lipiodol deposits in the target lesions (TL) within 24 hours after the initial TACE, 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 OS.

Results: The clinical-radiomics model predicted OS at 1, 2, and 3 years more accurately than the clinical or radiomics model alone (training group, AUC = 0.787, 0.765 and 0.827, respectively; validation group, AUC = 0.731, 0.713 and 0.798, respectively). The predicted high-risk subgroup based on the clinical-radiomics model had shorter mOS than predicted low-risk subgroup (training group, 16 m vs 37 m, p = 0.0002; validation group 14 m vs 35 m, p<0.0001), enabling risk stratification of various clinical subgroups.

Conclusion: The radiomic signature derived from lipiodol within 24 hours post-TACE functions as a prognostic biomarker for OS in HCC patients. The clinical-radiomics model demonstrates robust predictive performance, providing a valuable tool for prognostic evaluation in HCC.