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Background: Cancer-associated fibroblasts (CAFs) are the key components of the immune barrier in liver cancer. Therefore, gaining a deeper understanding of the heterogeneity and intercellular communication of CAFs holds utmost importance in boosting immunotherapy effectiveness and improving clinical outcomes. Methods: A comprehensive analysis by combing single-cell, bulk, and spatial transcriptome profiling with multiplexed immunofluorescence was conducted to unravel the complexities of CAFs in liver cancer. Results: Through an integrated approach involving 235 liver cancer scRNA-seq samples encompassing over 1.2 million cells, we found that CAFs were particularly increased in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). FAP + fibroblasts were identified as the dominant subtype of CAFs, and which were mainly involved in extracellular matrix organization and angiogenesis. These CAFs were enriched in the tumor boundary of HCC, but diffusely scattered within ICC. The DAB2 + and SPP1 + tumor-associated macrophages (TAMs) reinforce the function of FAP + CAFs through signals such as TGF-ß, PDGF, and ADM. Notably, the interaction between DAB2 + TAMs and FAP + CAFs promoted the formation of immune barrier and correlated with poorer patient survival, non-response to immunotherapy in HCC. High FAP and DAB2 immunohistochemical scores predicted shorter survival and higher serum AFP concentration in a local clinical cohort of 90 HCC patients. Furthermore, this communication pattern might be applicable to other solid malignancies as well. Conclusions: The interaction between DAB2 + TAMs and FAP + CAFs appears crucial in shaping the immune barrier. Strategies aimed at disrupting this communication or inhibiting the functions of FAP + CAFs could potentially enhance immunotherapy effectiveness and improve clinical outcomes.
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Fibroblastos Asociados al Cáncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Microambiente Tumoral/inmunología , Macrófagos/metabolismo , Macrófagos/inmunología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Colangiocarcinoma/inmunología , Colangiocarcinoma/metabolismo , Inmunoterapia/métodos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Masculino , Femenino , EndopeptidasasRESUMEN
OBJECTIVE: Meta-analysis was used to assess the efficacy and safety of ultrasound-guided radiofrequency ablation combined with transhepatic artery embolization chemotherapy for hepatocellular carcinoma. METHODS: Randomized controlled studies on ultrasound-guided radiofrequency ablation combined with transhepatic artery embolization chemotherapy for hepatocellular carcinoma were searched in the databases of PubMed, Embase, Cochrane library, web of science with a search deadline of March 14, 2024. Data were analyzed using Stata 15.0. RESULT: Six randomized controlled studies involving 520 individuals were finally included, the results of meta-analysis showed that ultrasound-guided radiofrequency ablation combined with TACE can improve objective response rate [RR = 1.52, 95%CI (1.28, 1.81)], improve disease control rate [RR = 1.15, 95%CI (1.06, 1.24)], The survival rate [RR = 1.34, 95%CI (1.19,1.51)] did not increase adverse reactions [RR = 1.34, 95%CI (1.00,1.79)]. CONCLUSION: Based on the findings of the current study, ultrasound-guided radiofrequency ablation combined with TACE was found to improve the objective remission rate, disease control rate, and did not increase adverse events in patients with hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Humanos , Ablación por Radiofrecuencia/métodos , Quimioembolización Terapéutica/métodos , Resultado del Tratamiento , Terapia Combinada , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Biopsia Líquida/métodos , Manejo de la Enfermedad , Pronóstico , Epigénesis Genética , Animales , Microambiente TumoralRESUMEN
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play a pivotal role in immunosuppression and tumor progression in hepatocellular carcinoma (HCC). While various treatments like surgical resection, ablation, and radiotherapy have been studied for their effects on circulating MDSC frequencies in HCC patients, the findings remain inconclusive. Transarterial Chemoembolization (TACE) stands as the standard care for unresectable HCC, with Microparticle TACE (mTACE) gaining prominence for its capacity to induce significant tumor necrosis. However, the immunological ramifications of such pathological outcomes are scarcely reported. METHODS AND RESULTS: This study aims to elucidate the alterations in MDSC subtypes, specifically monocytic MDSCs (mMDSCs) and early-stage MDSCs (eMDSCs), post-mTACE and to investigate their clinical correlations in HCC patients. A cohort comprising 75 HCC patients, 16 liver cirrhosis patients, and 20 healthy controls (HC) was studied. Peripheral blood samples were collected and analyzed for MDSC subtypes. The study also explored the associations between MDSC frequencies and various clinical parameters in HCC patients. The frequency of mMDSCs was significantly elevated in the HCC group compared to liver cirrhosis and HC. Importantly, mMDSC levels were strongly correlated with aggressive clinical features of HCC, including tumor size, vascular invasion, and distant metastasis. Post-mTACE, a marked reduction in mMDSC frequencies was observed, while eMDSC levels remained stable. CONCLUSIONS: Our findings underscore the critical role of mMDSCs in HCC pathogenesis and their potential as a therapeutic target. The study also highlights the efficacy of mTACE in modulating the immunosuppressive tumor microenvironment, thereby opening new avenues for combinatorial immunotherapeutic strategies in HCC management.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Células Supresoras de Origen Mieloide , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Células Supresoras de Origen Mieloide/inmunología , Quimioembolización Terapéutica/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Micropartículas Derivadas de Células/inmunología , Micropartículas Derivadas de Células/metabolismo , Adulto , Microambiente Tumoral/inmunologíaRESUMEN
CD98, also known as SLC3A2, is a multifunctional cell surface molecule consisting of amino acid transporters. CD98 is ubiquitously expressed in many types of tissues, but expressed at higher levels in cancerous tissues than in normal tissues. CD98 is also upregulated in most hepatocellular carcinoma (HCC) patients; however, the function of CD98 in HCC cells has been little studied. In this study, we generated a panel of monoclonal antibodies (MAbs) against surface proteins on human embryonic stem cells (hESCs). NPB15, one of the MAbs, bound to hESCs and various cancer cells, including HCC cells and non-small cell lung carcinoma (NSCLC) cells, but not to peripheral blood mononuclear cells (PBMCs) and primary hepatocytes. Immunoprecipitation and mass spectrometry identified the target antigen of NPB15 as CD98. CD98 depletion decreased cell proliferation, clonogenic survival, and migration and induced apoptosis in HCC cells. In addition, CD98 depletion decreased the expression of cancer stem cell (CSC) markers in HCC cells. In tumorsphere cultures, the expression of CD98 interacting with NPB15 was significantly increased, as were known CSC markers. After cell sorting by NPB15, cells with high expression of CD98 (CD98-high) showed higher clonogenic survival than cells with low expression of CD98 (CD98-low) in HCC cells, suggesting CD98 as a potential CSC marker on HCC cells. The chimeric version of NPB15 was able to induce antibody-dependent cellular cytotoxicity (ADCC) against HCC cells in vitro. NPB15 injection showed antitumor activity in an HCC xenograft mouse model. The results suggest that NPB15 may be developed as a therapeutic antibody for HCC patients.
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Anticuerpos Monoclonales , Carcinoma Hepatocelular , Proteína-1 Reguladora de Fusión , Neoplasias Hepáticas , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Animales , Ratones , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/inmunología , Proteína-1 Reguladora de Fusión/metabolismo , Proteína-1 Reguladora de Fusión/inmunología , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/inmunología , Proliferación Celular , Línea Celular Tumoral , Apoptosis , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/inmunología , Cadena Pesada de la Proteína-1 Reguladora de FusiónRESUMEN
This meta-analysis aimed to evaluate the efficacy of sorafenib plus transcatheter arterial chemoembolization (TACE) in treating hepato-cellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Twelve randomized controlled trials published until 28th Sep 2022 were finally included. Of the total 1746 patients, of whom 458 received sorafenib and TACE treatment (Group S+TACE), and 1288 only underwent TACE (Group TACE), were enrolled. Outcomes including time to progression (TTP), objective response rate (ORR), disease control rate (DCR), overall survival (OS), survival rate (SR), and adverse reactions, were extracted. The OS (HR: 0.596, 95 %CI: 0.507-0.685, p < 0.001; I2 = 0.0 %) and TTP (HR: 0.379, 95 %CI: 0.205-0.553, p < 0.001; I2 = 4.5 %) in the S+TACE group were longer than those in the TACE group. The ORR (RR: 2.101, 95 %CI: 1.555-2.839, p < 0.001; I2 = 0.0 %), DCR (RR: 1.547, 95 %CI: 1.126-2.126, p = 0.007; I2 = 79.6 %) and SR (RR: 1.416, 95 %CI: 1.183-1.694, p < 0.001; I2 = 83.8 %) in the S+TACE group were higher than those in the TACE group. Compared with the TCAE group, the higher odds of HFSR, oral ulcer, and diarrhea among patients with HCC complicated by PVTT were discovered in the S+TACE group. The marginal significance was found in ascites and gastrointestinal bleeding between the two groups. Sorafenib plus TACE has good efficacy and mild adverse reactions, which may be worthy of clinical promotion.
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Antineoplásicos , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Vena Porta , Ensayos Clínicos Controlados Aleatorios como Asunto , Sorafenib , Trombosis de la Vena , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/complicaciones , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/efectos adversos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Sorafenib/administración & dosificación , Sorafenib/uso terapéutico , Sorafenib/efectos adversos , Humanos , Trombosis de la Vena/terapia , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Resultado del Tratamiento , Terapia Combinada , Tasa de SupervivenciaRESUMEN
Background: Locoregional treatment combined with systemic therapy is expected to play a synergistic anticancer role. We conducted this systemic meta-analysis to examine the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib with or without programmed cell death protein-1 (PD-1) inhibitors (TLP group) compared with TACE + lenvatinib (TL group) for unresectable hepatocellular carcinoma (uHCC). Methods: From the inception date to April 2024, the data from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials. gov were used for meta-analysis. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CI) were used to measure the pooled effect. Results: This study included 10 retrospective cohort studies, including 1128 patients. The OS (HR=0.51; 95% CI: 0.43-0.60, Pâ<â0.05), PFS (HR=0.52; 95% CI: 0.45-0.61, Pâ<â0.05), ORR (RR = 1.58; 95% CI: 1.37-1.83; P < 0.05) and DCR (RR = 1.31; 95% CI: 1.20-1.43; P < 0.05) were significantly higher in TLP group than in the TL group. The incidence of AEs was acceptable. Prognostic factor analysis identified that ECOG PS (1/0), Child-Pugh class (B/A), BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for OS. BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for PFS. Conclusion: The TLP group had better efficacy for uHCC than that of the TL group, with acceptable safety. Systematic review registration: PROSPERO, identifier (CRD42023420093).
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/efectos adversos , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Quinolinas/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia CombinadaRESUMEN
BACKGROUND: Our research endeavored to develop a robust predictive signature grounded in super-enhancer-related genes (SERGs), with the dual objectives of forecasting survival outcomes and evaluating the tumor immune microenvironment (TiME) in hepatocellular carcinoma (HCC). METHODS: HCC RNA-sequencing data were retrieved from The Cancer Genome Atlas (TCGA), and 365 patients were randomly assigned to training or testing sets in 1:1 ratio. SERGs of HCC were downloaded from Super-Enhancer Database (SEdb). On the basis of training set, a SERGs signature was identified, and its prognostic value was confirmed by internal and external validation (GSE14520) sets. We subsequently examined the model for potential functional enrichment and the degree of tumor immune infiltration. Additionally, we carried out in vitro experiments to delve into the biological functions of CBX2 gene. RESULTS: An SE-related prognostic model including CBX2, TPX2, EFNA3, DNASE1L3 and SOCS2 was established and validated. According to this risk model, patients in the high-risk group had a significantly worse prognosis, and their immune cell infiltration was significantly different from that of low-risk group. Moreover, the high-risk group exhibited a significant enrichment of tumor-associated pathological pathways. The SERGs signature can generally be utilized to screen HCC patients who are likely to respond to immunotherapy, as there is a positive correlation between the risk score and the Tumor Immune Dysfunction and Exclusion (TIDE) score. Furthermore, the downregulation of the CBX2 gene expression was found to inhibit HCC cell viability, migration, and cell cycle progression, while simultaneously promoting apoptosis. CONCLUSIONS: We developed a novel HCC prognostic model utilizing SERGs, indicating that patients with high-risk score not only face a poorer prognosis but also may exhibit a diminished therapeutic response to immune checkpoint inhibitors (ICIs). This model is designed to tailor personalized treatment strategies to the individual needs of each patient, thereby improving the overall clinical outcomes for HCC patients. Furthermore, CBX2 is a promising candidate for therapeutic intervention in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Medicina de Precisión , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Pronóstico , Medicina de Precisión/métodos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Femenino , Masculino , Elementos de Facilitación Genéticos , Línea Celular Tumoral , Proliferación CelularRESUMEN
Hepatocellular carcinoma (HCC) is a highly aggressive cancer with a poor prognosis. The molecular mechanisms underlying its development remain unclear. Recent studies have highlighted the crucial role of RNA modifications in HCC progression, which indicates their potential as therapeutic targets and biomarkers for managing HCC. In this review, we discuss the functional role and molecular mechanisms of RNA modifications in HCC through a review and summary of relevant literature, to explore the potential therapeutic agents and biomarkers for diagnostic and prognostic of HCC. This review indicates that specific RNA modification pathways, such as N6-methyladenosine, 5-methylcytosine, N7-methylguanosine, and N1-methyladenosine, are erroneously regulated and are involved in the proliferation, autophagy, innate immunity, invasion, metastasis, immune cell infiltration, and drug resistance of HCC. These findings provide a new perspective for understanding the molecular mechanisms of HCC, as well as potential targets for the diagnosis and treatment of HCC by targeting specific RNA-modifying enzymes or recognition proteins. More than ten RNA-modifying regulators showed the potential for use for the diagnosis, prognosis and treatment decision utility biomarkers of HCC. Their application value for HCC biomarkers necessitates extensive multi-center sample validation in the future. A growing number of RNA modifier inhibitors are being developed, but the lack of preclinical experiments and clinical studies targeting RNA modification in HCC poses a significant obstacle, and further research is needed to evaluate their application value in HCC treatment. In conclusion, this review provides an in-depth understanding of the complex interplay between RNA modifications and HCC while emphasizing the promising potential of RNA modifications as therapeutic targets and biomarkers for managing HCC.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Procesamiento Postranscripcional del ARN , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico , Biomarcadores de Tumor/metabolismo , Animales , Regulación Neoplásica de la Expresión Génica , Pronóstico , ARN/genética , ARN/metabolismoRESUMEN
Transarterial chemoembolization (TACE) is an established therapeutic strategy for intermediate stage Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC). However, patients who are early refractory to TACE may not benefit from repeated TACE treatment. Our primary objective was to assess the diagnostic value of inflammatory markers in identifying early TACE refractory for patients with early (BCLC 0 and A) or intermediate (BCLC B) stage HCC. We retrospectively reviewed the HCC patients who underwent TACE as the initial treatment in two hospitals. Patients with early TACE refractoriness had significantly poorer median overall survival (OS) (16 vs 40 months, P<0.001) and progression-free survival (PFS) (7 vs 23 months, P<0.001) compared to TACE non-refractory patients. In the multivariate regression analysis, tumor size (P<0.001), bilobular invasion (P=0.007), high aspartate aminotransferase-to-platelet ratio index (APRI) (P=0.007), and high alpha fetoprotein (AFP) level (P=0.035) were independent risk factors for early TACE refractoriness. The predictive model showcasing these factors exhibited high ability proficiency, with an area under curve (AUC) of 0.833 (95%CI=0.774-0.892) in the training cohort, 0.750 (95%CI: 0.640-0.861) in the internal-validation cohort, and 0.733 (95%CI: 0.594-0.872) in the external-validation cohort. Calibration curve analysis revealed good agreement between the actual and predicted probabilities of early TACE refractoriness. Our preliminary study estimated the potential value of inflammatory markers in predicting early TACE refractoriness and provides a predictive model to assist in identifying patients who may not benefit from repeat TACE treatment.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/diagnóstico , Quimioembolización Terapéutica/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Biomarcadores de Tumor/sangre , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Adulto , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/metabolismoRESUMEN
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an important etiology of hepatocellular carcinoma (HCC), and there is no established therapy for this syndrome. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD(NET)) is an extremely rare syndrome considered to be life-threatening, with death occurring around 10 years of age. We present the oldest known autopsy case of this syndrome that developed HCC. This case provided important information on not only improving the course of this syndrome, but also understanding the natural history and therapeutic modalities of NASH and HCC. METHODS: The patient was diagnosed with ROHHAD(NET) syndrome in childhood, and liver cirrhosis due to NASH was diagnosed at age 17. HCC was detected at age 20, and embolization and irradiation were performed. At age 21, she died from accidental acute pancreatitis and subsequent liver failure and pulmonary hemorrhage. RESULTS: Rapid onset of obesity, hypoventilation, and hypothalamic disturbance appeared in childhood and was diagnosed as this syndrome. At age 17, liver cirrhosis due to NASH was diagnosed by liver biopsy, and at age 20, HCC was diagnosed by imaging. Transarterial chemoembolization and irradiation were performed, and the HCC was well controlled for a year. CONCLUSION: At age 21, she died from accidental acute pancreatitis, subsequent liver failure and pulmonary hemorrhage. Autopsy revealed that the HCC was mostly necrotized. This case was valuable not only for other ROHHAD(NET) syndrome cases, but also in improving our understanding of the natural history of NASH and HCC.
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Autopsia , Carcinoma Hepatocelular , Enfermedades Hipotalámicas , Hipoventilación , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Femenino , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/terapia , Hipoventilación/etiología , Hipoventilación/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedades Hipotalámicas/complicaciones , Enfermedades Hipotalámicas/diagnóstico , Obesidad/complicaciones , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Resultado Fatal , Adulto Joven , Enfermedades del Sistema Nervioso Autónomo/etiología , SíndromeRESUMEN
Hepatocellular carcinoma (HCC) is a highly heterogeneous kind of malignant tumor with a high recurrence rate and low five-year survival rate, which has become one of the major public health issues in China. Currently, HCC is the only solid tumor that can be solely diagnosed based on epidemiological history and typical imaging features without preoperative pathological confirmation. The paradigm for HCC imaging diagnosis has shifted in recent years from anatomy to function, from macroscopic to microscopic, and from diagnosis to prediction in the context of precision medicine, making it possible to study the microscopic processes such as HCC genes and their metabolic laws from the perspective of qualitative and quantitative imaging, thereby providing more accurate biological and imaging information for elucidating the occurrence, development, and clinical treatment decisions of HCC.This paper reviews the research progress of HCC imaging in recent years, demonstrating the rapid horizontal development and enormous potential of imaging in the vertical follow-up of HCC precision diagnosis and treatment. Simultaneously, it also puts forward the shortcomings of current HCC imaging research and looks forward to future development directions in order to be more accurately used in clinical decision support systems.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
Hepatocellular carcinoma (HCC) presents a significant global health burden, with alarming statistics revealing its rising incidence and high mortality rates. Despite advances in medical care, HCC treatment remains challenging due to late-stage diagnosis, limited effective therapeutic options, tumor heterogeneity, and drug resistance. MicroRNAs (miRNAs) have attracted substantial attention as key regulators of HCC pathogenesis. These small non-coding RNA molecules play pivotal roles in modulating gene expression, implicated in various cellular processes relevant to cancer development. Understanding the intricate network of miRNA-mediated molecular pathways in HCC is essential for unraveling the complex mechanisms underlying hepatocarcinogenesis and developing novel therapeutic approaches. This manuscript aims to provide a comprehensive review of recent experimental and clinical discoveries regarding the complex role of miRNAs in influencing the key hallmarks of HCC, as well as their promising clinical utility as potential therapeutic targets.
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Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , Animales , Biomarcadores de Tumor/genéticaRESUMEN
PURPOSE: To evaluate outcomes including safety and efficacy of drug-eluting bead trans-arterial chemo-embolization (DEB-TACE) in the treatment of locally advanced hepatocellular carcinoma (LA-HCC). MATERIALS AND METHODS: In this single-center, retrospective study, we evaluated 471 consecutive patients with LA-HCC who underwent DEB-TACE from 2015 to 2020. Efficacy of DEB-TACE was assessed based on the imaging response using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the biochemical response using alpha-fetoprotein (AFP) levels at 1-month follow-up. Adverse events, progression free survival (PFS), and overall survival were also examined. RESULTS: HCC distribution was bilobar in 49% with largest lesion mean size of 4.3 cm ± 3.2, and a majority of patients (46.7%) were Barcelona Club Liver Cancer (BCLC) stage B. Complete radiologic response was achieved in 120 (25.5%) patients, comparable to a reported 28% rate for conventional TACE. Biochemically, 41 (8.7%) patients achieved complete response, and 113 (24%) had a partial response. A total of 59 (12.5%) patients were successfully bridged to liver transplantation. Major adverse events were observed in 3%, while 7.2% experienced post-embolization syndrome. Mean PFS was 6.7 months ± 6.6, and overall survival was 64%, 16.3%, 2.1% at 1, 3, and 5 years, respectively. CONCLUSION: Based on our real world experience at a single center, DEB-TACE remains the locoregional therapy of choice for LA-HCC due to its favorable safety and efficacy profile.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Quimioembolización Terapéutica/métodos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Adulto , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análisisRESUMEN
Hepatocellular carcinoma (HCC) is a serious health issue due to its low early diagnosis rate, resistance to chemotherapy, and poor five-year survival rate. Therefore, it is crucial to explore novel diagnostic and therapeutic approaches tailored to the characteristics of HCC. Aggregation-induced emission (AIE) is a phenomenon where the luminescence of certain molecules, typically non-luminescent or weakly luminescent in solution, is significantly enhanced upon aggregation. AIE has been extensively applied in bioimaging, biosensors, and therapy. Fluorophore materials based on AIE (AIEgens) have a wide range of application scenarios and potential for clinical translation. This review focuses on recent advances in AIE-based strategies for diagnosing and treating HCC. First, the specific functional mechanism of AIE is described. Next, we summarize recent progress in the application of AIE for multimodal imaging, biosensor detection, and phototherapy. Finally, prospects and challenges for the AIE-based application in the diagnosis and therapy of HCC are discussed.
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Técnicas Biosensibles , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagen , Humanos , Técnicas Biosensibles/métodos , Colorantes Fluorescentes/química , Animales , Fototerapia , Imagen Óptica/métodos , Imagen Multimodal/métodosRESUMEN
Hepatocellular carcinoma (HCC) tissue is rich in dendritic cells, T cells, B cells, macrophages, natural killer cells and cellular stroma. Together they form the tumor microenvironment (TME), which is also rich in numerous cytokines. Tumorassociated macrophages (TAMs) are involved in the regulation of tumor development. TAMs in HCC receive stimuli in different directions, polarize in different directions and release different cytokines to regulate the development of HCC. TAMs are mostly divided into two cell phenotypes: M1 and M2. M1 TAMs secrete proinflammatory mediators, and M2 TAMs secrete a variety of antiinflammatory and protumorigenic substances. The TAM polarization in HCC tumors is M2. Both direct and indirect methods for TAMs to regulate the development of HCC are discussed. TAMs indirectly support HCC development by promoting peripheral angiogenesis and regulating the immune microenvironment of the TME. In terms of the direct regulation between TAMs and HCC cells, the present review mainly focuses on the molecular mechanism. TAMs are involved in both the proliferation and apoptosis of HCC cells to regulate the quantitative changes of HCC, and stimulate the related invasive migratory ability and cell stemness of HCC cells. The present review aims to identify immunotherapeutic options based on the mechanisms of TAMs in the TME of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Macrófagos Asociados a Tumores , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Inmunoterapia/métodosAsunto(s)
Carcinoma Hepatocelular , Resistencia a Antineoplásicos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/inmunología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéuticoRESUMEN
BACKGROUND: Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. METHODS: Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. RESULTS: Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. CONCLUSIONS: Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.