Oncogenic pathways refine a new perspective on the classification of hepatocellular carcinoma.

BACKGROUND: Genetic alterations in oncogenic pathways are critical for cancer initiation, development, and treatment resistance. However, studies are limited regarding pathways correlated with prognosis, sorafenib, and transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). METHODS: In this study, 1928 patients from 11 independent datasets and a clinical in-house cohort were screened to explore the relationships among canonical pathway alterations in HCC patients. The molecular mechanisms, biological functions, immune landscape, and clinical outcomes among three heterogeneous phenotypes were further explored. RESULTS: We charted the detailed landscape of pathway alterations in the TCGA-LIHC cohort, screened three pivotal pathways (p53, PI3K, and WNT), identified co-occurrence patterns and mutual exclusively, and stratified patients into three altered-pathway dominant phenotypes (ADPs). P53|PI3K ADP characterized by genomic instability (e.g., highest TMB, FGA, FGG, and FGL) indicated an unfavorable prognosis. While, patients in WNT ADP suggested a median prognosis, enhanced immune activation, and sensitivity to PD-L1 therapy. Remarkably, sorafenib and TACE exhibited efficacy for patients in WNT ADP and low frequent alteration phenotype (LFP). Additionally, ADP could work independently of common clinical traits (e.g., AJCC stage) and previous molecular classifications (e.g., iCluster, serum biomarkers). CONCLUSIONS: ADP provides a new perspective for identifying patients at high risk of recurrence and could optimize precision treatment to improve the clinical outcomes in HCC.

Machine Learning-Based Development of Nomogram for Hepatocellular Carcinoma to Predict Acute Liver Function Deterioration After Drug-Eluting Beads Transarterial Chemoembolization.

RATIONALE AND OBJECTIVES: Acute liver function deterioration (ALFD) following drug-eluting beads transarterial chemotherapy embolism (DEB-TACE) was considered a risk factor for prognosis in patients with hepatocellular carcinoma (HCC). In this study, we aimed to develop and validate a nomogram for the prediction of ALFD after DEB-TACE. MATERIALS AND METHODS: A total of 288 patients with HCC from a single center were randomly divided into a training dataset (n = 201) and a validation dataset (n = 87). The univariate and multivariate logistic regression analyses were performed to determine risk factors for ALFD. The least absolute shrinkage and selection operator (LASSO) was applied to identify the key risk factors and fit a model. The performance, calibration, and clinical utility of the predictive nomogram were assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). RESULTS: LASSO regression analysis determined six risk factors with fibrosis index based on four factors (FIB-4) as the independent factor for the occurrence of ALFD after DEB-TACE. Gamma-glutamyltransferase, FIB-4, tumor extent, and portal vein invasion were integrated into the nomogram. In both the training and validation cohorts, the nomogram demonstrated promising discrimination with AUC of 0.762 and 0.878, respectively. The calibration curves and DCA revealed good calibration and clinical utility of the predictive nomogram. CONCLUSION: The nomogram-based risk of ALFD stratification may improve clinical decision-making and surveillance protocols for patients with a high risk of ALFD after DEB-TACE.

[Analysis of curative effects of chemoembolization with drug-loaded microspheres of different particle sizes for the treatment of hepatocellular carcinoma].

Objective: To compare and analyze the clinical curative effect and safety of chemoembolization with drug-loaded microspheres of different particle sizes (D-TACE) for the treatment of hepatocellular carcinoma. Methods: Clinical data of 281 cases with hepatocellular carcinoma treated with drug-loaded microspheres-transarterial chemoembolization (TACE) were retrospectively analyzed. According to the different particle sizes of drug-loaded microspheres, they were divided into 100~300 µm (small particle size) and 300~500 µm (large particle size) group. Tumor response rate and complication conditions at 1, 3, and 6 months after chemoembolization were compared. The overall survival time of the two groups were analyzed. Quantitative data conformed to normal distribution and homogeneity of variance were compared using t-test, while other with Wilcoxon signed rank-sum test. Qualitative data were compared using χ2 test. Kaplan-Meier method was used for survival analysis, and the differences in survival were analyzed using Log-rank test. P＜0.05 was considered as statistically significant. Survival curves and histograms were drawn using GraphPad Prism9.1 software. Results: The complete remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 31.25%, 30.15%, and 42.45% and 18.25%, 15.79% and 24.74%, respectively, and the differences were statistically significant between groups (P1 month=0.012, P3 month=0.009, P6 month=0.008, P＜0.05). The objective remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 88.19%, 76.99%, and 70.75% and 81.02%, 72.81% and 53.60%, respectively. Six months after surgery, the small particle size group (objective response rate = 70.75%) was significantly higher than the large particle size group (objective response rate=53.6%, P=0.012). The disease control rates of the small particle size group were 95.14%, 83.33%, and 74.53%, while large particle size group were 91.24%, 81.58%, and 64.95%, respectively, with no statistically significant difference between the two groups. However, the incidence of postoperative biliary tumors (6.20%) was significantly higher in the small-size than large-size group (0.70%), and the difference was statistically significant (P＜0.05, P=0.03). There were no statistically significant differences between other adverse events such as post-embolization syndrome, liver abscess, and myelosuppression. The median survival time of the small and large particle size groups was 31.8 months and 20.5 months, respectively, but the difference was not statistically significant (P=0.182). Conclusions: In the treatment of hepatocellular carcinoma with D-TACE, the short-term curative effect of the small particle size group was better than large particle size group, but the incidence of biliary tumors was high, and D-TACE of different particle sizes had no significant effect on long-term survival.