Journal of Hepatocellular Carcinoma最新文献

Purpose: To evaluate the efficacy of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) for both primary and recurrent early-stage hepatocellular carcinoma (HCC) and to analyze the significant prognostic factors.

Patients and methods: Data from patients with early-stage primary or recurrent HCC who underwent TACE plus RFA between August 2019 and May 2024 were collected from three major general hospitals. 158 patients were divided into a primary group and a recurrent group on the basis of their baseline characteristics. Compared the objective response rate (ORR), 1-, 3-, and 5-year progression-free survival (PFS) rates, 1-, 3-, and 5-year overall survival (OS) rates, and complication rate between the two groups. Multivariate analyses were used to evaluate the factors influencing PFS and OS.

Results: One hundred fifty-eight patients were enrolled. The ORRs of the primary and recurrent groups were 98.2% and 95.1%, respectively, with no statistically significant difference (χ²= 2.032, Ρ = 0.362). The primary group having a significantly longer PFS time than the recurrent group (Ρ < 0.001). However, there was no significant difference in the 1-, 3-, and 5-year OS rates between the two groups (Ρ = 0.218). Multivariate analysis revealed that primary or recurrent HCC and the Child‒Pugh score were significant prognostic factors for PFS, whereas the serum albumin level was a significant prognostic factor for OS.

Conclusion: TACE plus RFA has similar clinical efficacy and safety for both primary and recurrent early HCC. Compared with patients with primary HCC, those with recurrent disease had significantly shorter PFS times.

Purpose: Hepatocellular Carcinoma (HCC) features a complex pathophysiology and unpredictable immunosuppressive microenvironment, which limit the effectiveness of traditional therapies and lead to poor patient outcomes. Understanding the immune characteristics of HCC is essential for elucidating the immune microenvironment and developing more effective treatments. This study investigates the role of Peptidyl-prolyl isomerase H (PPIH) in HCC by analyzing its expression, prognosis, methylation levels, and relationship with immune cell infiltration.

Methods: We utilized bulk sequencing and clinical data from UCSC Xena and the GTEx database for preprocessing and subsequent differential expression analysis of PPIH in tumor and adjacent normal tissues, evaluating prognostic parameters like overall survival and disease-free interval between low and high PPIH expression groups. Immune infiltration was analyzed via CIBERSORT and ssGSEA, while DNA methylation and somatic mutation analyses were performed using MExpress and "maftools", respectively, alongside in vitro and in vivo experiments to assess PPIH's functional roles.

Results: Our findings indicated that PPIH is significantly upregulated in various cancer types, correlating with poor patient prognosis, increased somatic mutations, and altered gene methylation patterns. High PPIH levels were linked to enhanced T regulatory (Treg) cell infiltration and a decline in Th17 cell populations, impacting vital pathways related to DNA damage repair and tumor proliferation. Furthermore, PPIH knockdown in vitro led to reduced cell viability, proliferation, and invasion while promoting apoptosis. In vivo, PPIH knockdown repressed tumor growth and modified the immune microenvironment by attenuating Th17 cell infiltration and potentially increasing Treg cell accumulation.

Conclusion: This study emphasizes PPIH's critical role in HCC progression by facilitating tumor growth and survival while modulating the immune landscape, thereby positioning PPIH as a potential therapeutic target for HCC management.

Purpose: Oxymatrine has potent anti-cancer activity, but its exact mechanism in liver cancer remains elusive. The present study was designated to explore oxymatrine's effect and the potential mechanism on Programmed cell death-ligand 1 (PD-L1) expression and ferroptosis in liver cancer.

Methods: Oxymatrine's influence on PD-L1 expression and ferroptosis-related proteins in liver cancer cells was explored in vitro and in vivo utilizing Western blotting, qRT-PCR, immunofluorescence, ELISA, H&E staining, immunohistochemistry, as well as detection of Fe²⁺, ROS, and MDA.

Results: The in-vivo results showed that xenotransplanted tumor mice with drug interventions (oxymatrine, anti-PD-L1, and combination groups) exhibited inhibited tumor growth compared to control mice. Relative to anti-PD-L1 administration alone, the combined treatment inhibited tumor growth more significantly, along with reduced interferon-γ (IFN-γ) expression in peripheral blood and remarkably increased tumor immune lymphocyte (CD4⁺ T and CD8⁺ T) infiltration in cancer tissues. Meanwhile, PD-L1, xCT, and GPX4 protein levels in the combination group were significantly downregulated. According to the in vitro results, IFN-γ promoted PD-L1, xCT, and GPX4 protein levels in liver cancer cell lines. Oxymatrine reversed IFN-γ-induced upregulation of PD-L1 expression; moreover, it downregulated xCT and GPX4 protein levels in liver cancer cells and promoted intracellular Fe²⁺, ROS, and MDA levels.

Conclusion: Oxymatrine promotes tumor immune response and ferroptosis in liver cancer by downregulating IFN-γ and synergistically enhances the inhibitory effect of anti-PD-L1 on liver cancer.

Objective: The objective of this study was to investigate the long-term outcomes between laparoscopic anatomical liver resection (LAR) and laparoscopic non-anatomical liver resection (LNAR) in patients with hepatocellular carcinoma (HCC).

Methods: In this single-center retrospective cohort study, 1773 patients, from January 2009 to December 2017, were assessed for inclusion. After exclusions, 661 patients were included: 304 patients received LAR and 357 patients received LNAR. Propensity score matching (PSM) with 1:1 ratio was used to eliminate the selection bias between LAR and LNAR groups. The Kaplan-Meier and Cox models were used for survival analysis.

Results: After PSM, 250 patients were in LAR or LNAR group, respectively. The overall survival (OS) had no significant difference between LAR and LNAR by Kaplan-Meier analysis. While, LAR had better disease-free survival (DFS) compared with LNAR (Log-rank P=0.035). The cumulative 5-year DFS rates were 48% for LAR, and 38% for LNAR. By Cox analysis, LAR was an independent risk factor of DFS (HR=1.308, P=0.030). In subgroup analysis for tumor size ≤ 5 cm, 207 patients were in LAR or LNAR subgroup after PSM. LAR had better DFS compared with LNAR (Log-rank P=0.033). LAR was an independent risk factor of DFS (HR=1.333, P=0.036). The cumulative 5-year DFS rates were 50% for LAR, and 39% for LNAR. In another subgroup analysis for tumor size > 5 cm, 43 patients were in LAR or LNAR subgroup after PSM. The DFS had no significant difference between LAR and LNAR (Log-rank P=0.912).

Conclusion: LAR is preferred for HCC patients with tumor size ≤5cm compared with LNAR because of the better DFS. For patients with tumor size >5cm, LAR and LNAR might be alternative procedures with comparable long-term outcomes.

Purpose: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Oncofetal proteins are the optimal diagnostic biomarkers and therapeutic targets for HCC. As the most abundant modification in RNA, N⁶-methyladenosine (m⁶A) has been reported to be involved in HCC initiation and progression. However, whether m⁶A has oncofetal characteristics remains unknown.

Methods: Gene expression in HCC tissues and cells was detected using qPCR. The level of m⁶A methylation was determined using methylated RNA immunoprecipitation assay. The biological roles of NUTM2B-AS1 in HCC were detected using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, and spheroid formation assays. The mechanisms underlying the roles of NUTM2B-AS1 were explored using RNA immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP), chromatin immunoprecipitation (ChIP), and assay for transposase-accessible chromatin (ATAC).

Results: NUTM2B-AS1 was identified as a novel oncofetal long noncoding RNA that was upregulated in the fetal liver and HCC and silenced in adult liver tissues. METTL3 and METTL16 induce m⁶A hypermethylation of NUTM2B-AS1. The m⁶A methylation levels of NUTM2B-AS1 exhibit oncofetal characteristics. m⁶A methylation upregulates NUTM2B-AS1 expression by increasing NUTM2B-AS1 transcript stability. m⁶A-methylated NUTM2B-AS1 promotes HCC cell proliferation and stemness via epigenetically activating BMPR1A expression. NUTM2B-AS1 specifically binds to BMPR1A promoter. m⁶A-methylated NUTM2B-AS1 is recognized by the m⁶A reader YTHDC2, which further binds to the H3K4 methyltransferase MLL1. m⁶A-methylated NUTM2B-AS1 recruits YTHDC2 and MLL1 to BMPR1A promoter, leading to increased H3K4me3 and chromatin accessibility at BMPR1A promoter. Functional rescue assays suggest that BMPR1A is a critical mediator of the oncogenic role of m⁶A-methylated NUTM2B-AS1 in HCC.

Conclusion: METTL3- and METTL16-mediated m⁶A methylation of NUTM2B-AS1 is a novel oncofetal molecular event in HCC that promotes HCC stemness via epigenetically activating BMPR1A transcription.

Background: Macrotrabecular-massive (MTM) and vessels encapsulating tumor clusters (VETC)-hepatocellular carcinoma (HCC) are aggressive histopathological phenotypes with significant prognostic implications. However, the molecular markers associated with MTM-HCC and VETC-HCC and their implications for clinical outcomes and therapeutic strategies remain unclear.

Methods: Utilizing the TCGA-LIHC cohort, we employed machine learning techniques to develop a prognostic risk score based on MTM and VETC-related genes. The performance of the risk score was assessed by investigating various aspects including clinical outcomes, biological pathways, treatment responses, drug sensitivities, tumor microenvironment, and molecular subclasses. To validate the risk score, additional data from the ICGC-JP, GSE14520, GSE104580, GSE109211, and an in-house cohort were collected and analyzed.

Results: The machine learning algorithm established a 4-gene-based risk score. High-risk patients had significantly worse prognosis compared to low-risk patients, with the risk score being associated with malignant progression of HCC. Functionally, the high-risk group exhibited enrichment in tumor proliferation pathways. Additionally, patients in the low-risk group exhibited improved response to TACE and sorafenib treatments compared to the high-risk group. In contrast, the high-risk group exhibited reduced sensitivity to immunotherapy and increased sensitivity to paclitaxel. In the in-house cohort, high-risk patients displayed higher rates of early recurrence, along with an increased frequency of elevated alpha-fetoprotein, microvascular invasion, and aggressive MRI features associated with HCC.

Conclusion: This study has successfully developed a risk score based on MTM and VETC-related genes, providing a promising tool for prognosis prediction and personalized treatment strategies in HCC patients.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the third leading cause of cancer-related deaths. Imaging plays a crucial role in the screening, diagnosis, and monitoring of HCC; however, the potential mechanism regarding phenotypes or molecular subtyping remains underexplored. Radiomics significantly expands the selection of features available by extracting quantitative features from imaging data. Radiogenomics bridges the gap between imaging and genetic/transcriptomic information by associating imaging features with critical genes and pathways, thereby providing biological annotations to these features. Despite challenges in interpreting these connections, assessing their universality, and considering the diversity in HCC etiology and genetic information across different populations, radiomics and radiogenomics offer new perspectives for precision treatment in HCC. This article provides an up-to-date summary of the advancements in radiomics and radiogenomics throughout the HCC care continuum, focusing on the clinical applications, advantages, and limitations of current techniques and offering prospects. Future research should aim to overcome these challenges to improve the prognosis of HCC patients and leverage imaging information for patient benefit.

Background: Primary hepatic Neuroendocrine carcinoma (PHNEC) is exceptionally rare, and when it cannot be surgically removed locally, systemic combination therapy is the preferred treatment. However, current treatments have shown limited effectiveness, and more effective approach remains a matter of debate.

Case presentation: We present a case involving a female patient diagnosed with non-surgically suitable PHNEC, confirmed through pathology. Following four cycles of standard first-line systemic chemotherapy, this intervention was prompted by imaging indicating suboptimal local lesion control, the patient underwent localized interventional and microwave ablation therapy. Subsequently, an evaluation based on mRECIST criteria revealed complete remission post-procedure. The disease sustained this remission status throughout the 14-month follow-up, with the administration of 14 cycles of immunocheckpoint inhibitor maintenance therapy, showing no signs of local recurrence or distant metastasis and devoid of any associated complications.

Conclusion: This case introduces a novel therapeutic avenue for individuals who are ineligible for surgery and have not responded to systemic chemotherapy. The diagnosis and management of PHNEC are deliberated within the framework of this particular case.

Purpose: Transarterial chemoembolization (TACE) is recommended as a standard therapy for intermediate-stage hepatocellular carcinoma (HCC) and is the most widely used first-line treatment for advanced HCC. This study aimed to evaluate the clinical benefits and tolerability of TACE added to a combination of lenvatinib and programmed death-1 (PD-1) inhibitor in patients with unresectable HCC (uHCC).

Patients and methods: We conducted a retrospective cohort study involving 144 patients with uHCC treated between August 2020 and August 2023. Patients received a combination of lenvatinib and a PD-1 inhibitor with or without TACE (T+L+P, n=81 or L+P, n=63, respectively). The baseline characteristics of the two groups were compared, and propensity score matching (PSM) was used to minimize bias. The study endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Factors influencing survival rates were analyzed using Cox regression, and adverse events (AEs) were documented and assessed.

Results: Before PSM, the T+L+P group showed significantly higher ORR (64.1% vs 44.4%, p < 0.05), longer median PFS (14.3 vs 9.6 months, p < 0.05), and longer median OS (24.6 vs 19.5 months, p < 0.05) compared to the L+P group. Even post-PSM, the T+L+P group showed significantly better OS and PFS compared to the L+P group (mOS: 28.0 vs 17.6 months p=0.0011, mPFS: 15.8 vs 9.3 months, p < 0.05). Univariate and multivariate analyses identified treatment options as independent factors for PFS and OS. The safety profile of the T+L+P regimen was acceptableThe incidence and severity of adverse reactions in the T+L+P group were not significantly different compared to the L+P group (any grade, 90.1 vs 93.6%, p=0.551; grade≥3, 25.9 vs 23.8%, p=0.843).