Journal of Hepatocellular Carcinoma最新文献

Purpose: To predict the efficacy of patients treated with hepatectomy and transarterial chemoembolization (TACE) based on machine learning models using clinical and radiomics features.

Patients and methods: Patients with HCC whose first treatment was hepatectomy or TACE from June 2016 to July 2021 were collected in the retrospective cohort study. To ensure a causal effect of treatment effect and treatment modality, perfectly matched patients were obtained according to the principle of propensity score matching and used as an independent test cohort. Inverse probability of treatment weighting was used to control bias for unmatched patients, and the weighted results were used as the training cohort. Clinical characteristics were selected by univariate and multivariate analysis of cox proportional hazards regression, and radiomics features were selected using correlation analysis and random survival forest. The machine learning models (Death_hepatectomy and Death_TACE) were constructed to predict the probability of patient death after treatment (hepatectomy and TACE) by combining clinical and radiomics features, and an optimal treatment regimen was recommended. In addition, a prognostic model was constructed to predict the survival time of all patients.

Results: A total of 418 patients with HCC who received either hepatectomy (n=267, mean age, 58 years ± 11 [standard deviation]; 228 men) or TACE (n=151, mean age, 59 years ± 13 [standard deviation]; 127 men) were recruited. After constructing the machine learning models Death_hepatectomy and Death_TACE, patients were divided into the hepatectomy-preferred and TACE-preferred groups. In the hepatectomy-preferred group, hepatectomy had a significantly prolonged survival time than TACE (training cohort: P < 0.001; testing cohort: P < 0.001), and vise versa for the TACE-preferred group. In addition, the prognostic model yielded high predictive capability for overall survival.

Conclusion: The machine learning models could predict the outcomes difference between hepatectomy and TACE, and prognostic models could predict the overall survival for HCC patients.

Purpose: To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients.

Patients and methods: This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student's t test, χ2 test, and multivariable regression analysis.

Results: Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson-Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC.

Conclusion: Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.

Purpose: Alanine glyoxylate aminotransferase (AGXT) family members are crucial in cancer processes, but their role in hepatocellular carcinoma (HCC) metabolism is unclear. This study investigates AGXT2's function in HCC.

Patients and methods: AGTX2 expression was studied using bioinformatics, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), Western blot, and Enzyme-linked immunosorbent assay (ELISA). A lentivirus-induced AGTX2 overexpression cell model was analyzed with RNA sequencing (RNA-seq) and liquid chromatography-mass spectrometry (LC-MS). Cholesterol levels were confirmed by Oil Red O staining. AGTX2 effects were evaluated through cell cycle analysis, wound healing, and transwell migration assays.Tumorigenic effects were observed in NOD-SCID IL2Rγnull (NTG) mice in subcutaneous experiments. Protein interaction was examined through co-immunoprecipitation methods.

Results: We observed a significant reduction in AGXT2 mRNA and protein levels in both HCC tumor tissues and serum samples from patients with liver cancer, which was associated with a worse prognosis. The activation of AGXT2 has been shown to effectively decrease cholesterol levels in liver cancer cells, serving as an antagonist in the cholesterol metabolism pathway. An increase in low density lipoprotein receptor (LDLR) mRNA was noted in cells overexpressing AGXT2, accompanied by a decrease in LDLR protein and an elevation in proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and protein levels. Molecular docking and co-immunoprecipitation experiments further elucidated the interaction between AGXT2 and LDLR proteins. AGXT2 was observed to suppress the migratory and invasive capabilities of HCC cells, inducing cell cycle arrest in the G2/M phase. AGXT2 activation inhibited subcutaneous liver cancer tumor growth in NTG mice.

Conclusion: AGXT2 was found to lower cholesterol levels in liver cancer cells, possibly through interactions with the LDLR protein and modulation of PCSK9-mediated LDLR degradation. This mechanism may impede cholesterol transport to liver cancer cells, thereby suppressing their growth and metastasis.

Purpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib and tislelizumab (TACE-Len-T) versus TACE plus lenvatinib (TACE-Len) as the first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).

Patients and methods: This retrospective study included 136 uHCC patients treated with TACE-Len-T or TACE-Len from January 1, 2021, to June 30, 2023. Clinical outcomes including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs) were compared between the two groups. The risk factors affecting OS and PFS were also analyzed.

Results: The median OS and PFS of the TACE-Len-T group were significantly longer than those of the TACE-Len group (Median OS: not reached vs 13.8 months, P<0.001; Median PFS: 13.0 months vs 2.7 months, P<0.001). The best overall objective response rate (ORR) was also better with TACE-Len-T treatment (ORR: 72.1% vs 29.4%, P<0.001), and the disease control rate (DCR) significantly increased in the TACE-Len-T group (88.2% vs 48.5%, P<0.001). Multivariate analyses revealed that TACE-Len treatment, tumor number >3, and cTACE were independent risk factors for OS, whereas TACE-Len treatment was the only independent risk factor for PFS. The frequency and severity of AEs in the TACE-Len-T group were comparable to those in the TACE-Len group (any grade: 92.6% vs 91.2%, P=0.753; grade 3 or 4: 33.8% vs 32.3%, P=0.855).

Conclusion: TACE-Len-T treatment significantly improved OS, PFS, ORR, and DCR over TACE-Len treatment, with a manageable safety profile in uHCC.

Background: The prognosis of initially unresectable hepatocellular carcinoma (iuHCC) has been improved by TACE with TKIs and PD-1 inhibitors (TTP). However, the role of timing of tumor progression and and early salvage surgery during TTP therapy remains unclear.

Patients and methods: The data of 151 patients who received TTP for iuHCC consecutively between November 2019 and December 2022 were retrospectively analyzed. The X-Tile software was used to determine the optimal threshold of progression timing to differentiate the post-progression survival (PPS) for patients with tumor progression, ultimately yielding 9 months as the optimal cut-off time. Early tumor progression was defined as patients with tumor recurrence (surgical patients) or progressive disease by mRECIST (nonsurgical patients) within 9 months of initial treatment. Accordingly, early salvage surgery was defined as salvage surgery performed within 9 months of the initial treatment.

Results: Out of all the patients, 55 (36.4%) patients showed early tumor progression, 33 (34.4%) showed late tumor progression, and 63 (41.7%) showed non-progression. Patients who experienced early tumor progression had a median PPS of 5.2 months, while those with late tumor progression had a median PPS of 16.8 months (P < 0.001). Multivariable analysis revealed a robust independent correlation between early tumor progression and PPS (HR = 3.279, 95% CI: 1.591-6.756; P = 0.001). Patients who received early salvage surgery showed a considerably lower early tumor progression rate when compared with patients who did not receive early surgery (12.5% vs 42.9%, P = 0.002). The multivariable analysis revealed that early salvage surgery was an independent factor influencing early tumor progression (OR = 0.246; 95% CI: 0.078-0.773; P = 0.016).

Conclusion: Early tumor progression is associated with worse PPS in patients with iuHCC receiving TTP therapy. Early salvage surgery can further improve patient outcomes by lowering the incidence of early progression.

Background and aims: Six-monthly ultrasound surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. Surveillance enhances early detection and improves survival. Yet, despite clear benefits, uptake remains low. We aim to identify and explore ways to overcome patient-related barriers to HCC surveillance with the aim of producing invitations for surveillance.

Methods: Using the COM-B model of behaviour and a co-design process, we collaborated with patients, liver health charities and advocacy groups, to identify patient-related barriers to attending HCC surveillance. We performed qualitative thematic analysis of co-production workshops on HCC surveillance to develop information leaflets and surveillance invitations.

Results: Twenty-eight participants attended five workshops. Fear of a serious diagnosis and stigma from healthcare professionals were highlighted as main patient-related barriers to attending surveillance appointments. Co-design was used to develop informative, user-friendly, non-judgemental invitations and information regarding HCC surveillance relevant to populations with cirrhosis.

Conclusion: We identified potential patient barriers to surveillance uptake and developed patient facing material that directly addressed these barriers to be trialled in the clinic. Targeting patient-specific barriers may increase uptake of surveillance and therefore enhance early diagnosis.

Purpose: Hepatectomy could provide better survival benefit for hepatocellular carcinoma (HCC) with type I/II portal vein tumor thrombosis (PVTT). However, the postoperative recurrence remains high. We discussed whether neoadjuvant therapy could reduce HCC recurrence for these patients.

Patients and methods: One hundred and thirty-eight resectable HCC with type I-II PVTT were retrospectively included. The neoadjuvant therapy regimens included tyrosine kinase inhibitor (TKI), programmed death 1(PD-1) antibodies and transarterial chemoembolization (TACE). Short-term and long-term outcomes were compared. Propensity score matching (PSM) was performed to minimize the influence of potential confounders.

Results: Thirty-three patients underwent neoadjuvant therapy and 105 patients underwent surgery alone. In the neoadjuvant group, 7 (21.2%) patients achieved stable disease, 13 (39.4%) achieved partial response and 13 (39.4%) achieved complete response based on the modified Response Evaluation Criteria in Solid Tumors criterion. By PSM, the neoadjuvant therapy resulted in less microvascular invasion (24.1% vs 50.0%, P=0.021), satellite nodule (6.9% vs 24.1%, P=0.036) and less patients with alpha-fetoprotein>20(ng/mL) (37.9% vs 69.0%, P=0.006). The neoadjuvant therapy reduced tumor recurrence and prolonged survival. Multivariate analysis found that neoadjuvant therapy was an independent protective factor for overall survival and recurrence free survival.

Conclusion: Neoadjuvant treatment presents a promising treatment option for HCC patients with type I/II PVTT.

Purpose: Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored.

Methods: We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis.

Results: The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival.

Conclusion: The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.