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1.
Clin. transl. oncol. (Print) ; 26(3): 698-708, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230799

RESUMO

Purpose There is compelling evidence that long-stranded non-coding RNAs (lncRNAs) play an important role in the progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of lncRNA XXYLT1 antisense-2 (XXYLT1-AS2) in HCC progression. Methods Real-time PCR was used to assess the levels of XXYLT1-AS2 in plasma from HCC and normal patients. Cell proliferation, apoptosis, migration, and invasion were monitored, and tumor xenografts were established to investigate the biological functions of XXYLT1-AS2 by gain-of-function and loss-of-function studies in vitro and in vivo, the expression of autophagy biomarkers and transcriptional factor EB (TFEB) was examined by immunoprecipitation, ubiquitination assays, and western blotting. Autophagy inhibitor, 3-methyladenine (3MA), and proteasome inhibitor, MG132, were used to verify the role of autophagy in HCC progression and the effect of XXYLT1-AS2 on TFEB ubiquitination, respectively. Results In this study, we identified that lncRNA XXYLT1-AS2 is highly expressed in HCC plasma and promotes tumor growth in vivo. In functional studies, it was found that silent expression of XXYLT1-AS2 inhibited HCC proliferation, migration, invasion, and activated autophagy of HCC cells, which were attenuated by autophagy inhibitor, 3MA. Mechanistically, XXYLT1-AS2 decreased the protein level of TFEB through promoting its degradation by ubiquitin proteasome pathway. Conclusion XXYLT1-AS2 plays an oncogenic role in HCC progression through inhibition of autophagy via promoting the degradation of TFEB, and thus could be a novel target for HCC treatment (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Autofagia/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular
2.
Radiología (Madr., Ed. impr.) ; 66(1): 23-31, Ene-Feb, 2024. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-229643

RESUMO

Introducción: La evaluación de la respuesta del carcinoma hepatocelular (CHC) se basa actualmente en el realce en la fase arterial, que no tiene en cuenta los cambios microestructurales en el tumor después de la quimioembolización transarterial (TACE). Objetivo: Este estudio prospectivo se llevó a cabo para evaluar la viabilidad y la eficacia de la imagen de movimiento incoherente intravóxel (IVIM) en la evaluación de la respuesta de CHC después de TACE. A 39 pacientes cirróticos con 48 CHC se les realizó una resonancia magnética (RM) 1 semana antes y 6 semanas después de la TACE. Se midieron parámetros IVIM como Dlenta (difusión verdadera), Drápida (seudodifusión), la fracción de perfusión y el ADC antes y después de la TACE. Los valores antes y después de la TACE en las lesiones LR-TR no viables y viables según la clasificación LI-RADS de categorías de respuesta al tratamiento se compararon mediante pruebas t emparejadas. Se realizó un análisis de la curva ROC para calcular la sensibilidad y la especificidad y proponer valores de corte.Resultado: Las lesiones no viables mostraron un aumento significativo de la Dlenta (1,208±0,581 frente a 1,560±0,494, valor de p=–0,0207) y de ADC (1,37±0,53 frente a 1,65±0,4287, valor de p=–0,016) después de la TACE. También se observó una disminución significativa de los valores de Drápida (33,7±10,4 frente a 23,75±12,13, valor de p=0,0005) y f (19,92±10,54 frente a 12,9±10,41, valor de p=0,012) después de la TACE en las lesiones no viables en comparación con las viables. El cambio en la difusión verdadera tuvo el mayor AUC (0,741) entre los parámetros IVIM, con un aumento superior a 0,075 entre los valores previos y posteriores a la TACE, con una sensibilidad y especificidad del 81,8 y el 60%, respectivamente, para la respuesta completa. Conclusión: La IVIM es factible para evaluar la respuesta en el CHC después de la TACE. La difusión verdadera es más sensible y específica que la difusión aparente para...(AU)


Introduction: Response evaluation of hepatocellular carcinoma (HCC) currently is based on arterial phase enhancement which doesn’t take into microstructural changes in the tumor after trans-arterial chemoembolization (TACE). Aim: This prospective study was conducted to assess the feasibility and efficacy of intravoxel incoherent motion imaging (IVIM) in response evaluation of HCC after TACE. 39 cirrhotic patients with 48 HCC underwent MR imaging 1 week within and 6weeks after TACE. IVIM parameters like Dslow (true diffusion), Dfast (pseudodiffusion), perfusion fraction and ADC were measured prior to and postTACE. The pre and postTACE values in LR-TR (LIRADS-treatment response) nonviable and viable lesions were compared using paired t-tests. ROC curve analysis was done to calculate sensitivity and specificity and propose cut-off values. Result: Non-viable lesions showed a significant increase in Dslow (1.208±0.581 vs. 1.560±0.494, p-value –0.0207) and ADC (1.37±0.53 vs. 1.65±0.4287, p-value 0.016) after TACE. There was also significant decrease in Dfast (33.7±10.4 vs. 23.75±12.13, p-value 0.0005) and f (19.92±10.54 vs. 12.9±10.41, p-value 0.012) values after TACE in non-viable lesions compared to viable lesions. The change in true diffusion had the highest AUC (0.741) among IVIM parameters with greater than 0.075 increase between preTACE and postTACE values having a sensitivity and specificity of 81.8% and 60% respectively for complete response. Conclusion: IVIM imaging is feasible to assess the response in HCC after TACE. True diffusion is more sensitive and specific than apparent diffusion in evaluating the response.(AU)


Assuntos
Humanos , Masculino , Feminino , Carcinoma Hepatocelular/diagnóstico por imagem , Quimioembolização Terapêutica , Espectroscopia de Ressonância Magnética , Estudos Prospectivos , Radiologia , Diagnóstico por Imagem
3.
Clin. transl. oncol. (Print) ; 26(2): 326-337, feb. 2024.
Artigo em Inglês | IBECS | ID: ibc-230179

RESUMO

Hepatocellular carcinoma (HCC) caused by HBV, HCV infection, and other factors is one of the most common malignancies in the world. Although, percutaneous treatments such as surgery, ethanol injection, radiofrequency ablation, and transcatheter treatments such as arterial chemoembolization are useful for local tumor control, they are not sufficient to improve the prognosis of patients with HCC. External interferon agents that induce interferon-related genes or type I interferon in combination with other drugs can reduce the recurrence rate and improve survival in HCC patients after surgery. Therefore, in this review, we focus on recent advances in the mechanism of action of type I interferons, emerging therapies, and potential therapeutic strategies for the treatment of HCC using IFNs (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Prognóstico , Resultado do Tratamento
4.
Clin. transl. oncol. (Print) ; 26(2): 375-388, feb. 2024.
Artigo em Inglês | IBECS | ID: ibc-230183

RESUMO

Purpose Long noncoding RNAs (lncRNAs) with abnormal expression are frequently seen in hepatocellular cancer patients (HCC). Previous studies have reported the correlation between lncRNA and prognosis processes of HCC patients. In this research, a graphical nomogram with lncRNAs signatures, T, M phases was developed using the rms R package to estimate the survival rates of HCC patients in year 1, 3, and 5. Methods To find the prognostic lncRNA and create the lncRNA signatures, univariate Cox survival analysis and multivariate Cox regression analysis were chosen. The rms R software package was used to build a graphical nomogram based on lncRNAs signatures to predict the survival rates in of HCC patients in 1, 3, and 5 years. Using “edgeR”, “DEseq” R packages to find the differentially expressed genes (DEGs). Results Firstly, a total of 5581 DEGs including 1526 lncRNAs and 3109 mRNAs were identified through bioinformatic analysis, of which 4 lncRNAs (LINC00578, RP11-298O21.2, RP11-383H13.1, RP11-440G9.1) were identified to be strongly related to the prognosis of liver cancer (P < 0.05). Moreover, we constructed a 4-lncRNAs signature by using the calculated regression coefficient. 4-lncRNAs signature is identified to significantly correlated with clinical and pathological characteristics (such as T stage, and death status of HCC patients). Conclusions A prognostic nomogram on the base of 4-lncRNAs markers was built, which is capable to accurately predict the 1-year, 3-year, and 5-year survival of HCC patients after the construction of the 4-lncRNAs signature linked with prognosis of HCC (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Estimativa de Kaplan-Meier , Nomogramas , Prognóstico
5.
Clin. transl. oncol. (Print) ; 26(2): 496-514, feb. 2024.
Artigo em Inglês | IBECS | ID: ibc-230194

RESUMO

Background Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors, with a slow onset, rapid progression, and frequent recurrence. Previous research has implicated mitochondrial ribosomal genes in the development, metastasis, and prognosis of various cancers. However, further research is necessary to establish a link between mitochondrial ribosomal protein (MRP) family expression and HCC diagnosis, prognosis, ferroptosis-related gene (FRG) expression, m6A modification-related gene expression, tumor immunity, and drug sensitivity. Methods Bioinformatics resources were used to analyze data from patients with HCC retrieved from the TCGA, ICGC, and GTEx databases (GEPIA, UALCAN, Xiantao tool, cBioPortal, STRING, Cytoscape, TISIDB, and GSCALite). Results Among the 82 MRP family members, 14 MRP genes (MRPS21, MRPS23, MRPL9, DAP3, MRPL13, MRPL17, MRPL24, MRPL55, MRPL16, MRPL14, MRPS17, MRPL47, MRPL21, and MRPL15) were significantly upregulated differentially expressed genes (DEGs) in HCC tumor samples in comparison to normal samples. Receiver-operating characteristic curve analysis indicated that all 14 DEGs show good diagnostic performance. Furthermore, TCGA analysis revealed that the mRNA expression of 39 MRPs was associated with overall survival (OS) in HCC. HCC was divided into two molecular subtypes (C1 and C2) with distinct prognoses using clustering analysis. The clusters showed different FRG expression and m6A methylation profiles and immune features, and prognostic models showed that the model integrating 5 MRP genes (MRPS15, MRPL3, MRPL9, MRPL36, and MRPL37) and 2 FRGs (SLC1A5 and SLC5A11) attained a greater clinical net benefit than three other prognostic models. Finally, analysis of the CTRP and GDSC databases revealed several potential drugs that could target prognostic MRP genes (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Ribossômicas/genética , Biomarcadores Tumorais/genética , Antígenos de Histocompatibilidade Menor , Prognóstico , Proteínas de Transporte de Sódio-Glucose
6.
Clin. transl. oncol. (Print) ; 26(1): 155-170, jan. 2024.
Artigo em Inglês | IBECS | ID: ibc-229154

RESUMO

Background To compare the efficacy and safety between emergency hepatectomy (EH) and emergency transarterial embolization (TAE) followed by staged hepatectomy (SH) in the treatment of spontaneous ruptured hepatocellular carcinoma (rHCC). Methods Databases (PubMed, EMBASE, Web of science, Cochrane Library, ClinicalTrial.gov, CNKI, Wanfang and VIP) were searched for all relevant comparative studies from January 2000 to October 2020. Odds ratio (OR) and mean difference (MD) with 95% confidence interval (CI) were pooled for dichotomous and continuous variables, respectively. Subgroup analyses based on the kind of embolization were conducted. RevMan 5.3 software was adopted for meta-analysis. Results Eighteen studies with 871 patients were finally included in this meta-analysis, 448 in EH group and 423 in TAE + SH group. No significant difference was observed in successful hemostasis (P = 0.42), postoperative hospital stay (P = 0.12), complication rate (P = 0.08) between EH and TAE + SH group. However, TAE + SH group was associated with shorter operating time (P < 0.00001), fewer perioperative blood loss (P = 0.007), fewer blood transfusion (P = 0.003), lower in-hospital mortality (P < 0.00001) and higher 1-year survival as well as 3-year survival (P < 0.0001; P = 0.003) compared with EH group. Conclusion Compared with EH, TAE + SH could reduce perioperative operating time, blood loss, blood transfusion, mortality rate and increase the long-term survival rate of the rHCC patients, which may be a better treatment for resectable rHCC (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Ruptura Espontânea/patologia , Ruptura Espontânea/terapia , Resultado do Tratamento
7.
Gastroenterol. hepatol. (Ed. impr.) ; 46(10): 754-763, dic. 2023. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-228223

RESUMO

Background & aims: Life-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. Methods: 491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical–biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. Results: During a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01–1.05), age (HR, 1.04; 95% CI, 1.01–1.08) and albumin levels (HR, 0.90; 95% CI, 0.84–0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08–1.37) and albumin (HR, 0.90; 95% CI, 0.84–0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. (AU)


Antecedentes y objetivos: En pacientes con hepatitis C avanzada se recomienda la vigilancia del carcinoma hepatocelular (CHC) de por vida tras la respuesta viral sostenida (RVS). La identificación de pacientes que podrían interrumpir de manera segura el screening es esencial, por ello nuestro objetivo fue identificar subgrupos de pacientes con bajo riesgo de desarrollo de CHC. Métodos: Se realizó un seguimiento prospectivo de 491 pacientes con fibrosis avanzada y compensada (≥F3) tras la RVS obtenida con terapias libres de interferón. Se registraron parámetros clínico-biológicos y se midió la rigidez hepática mediante elastografía de transición (ET) antes del inicio del tratamiento y en la respuesta viral sostenida y se realizó screening para el desarrollo de CHC. Resultados: Durante una mediana de seguimiento de 49,8 meses, 29 (5,9%) pacientes desarrollaron CHC. (Tasa de incidencia: 1,6/100 pacientes-año [PA]). Se propusieron dos modelos predictivos basados en la puntuación de ET (Modelo-A) o FIB-4 (Modelo-B). Se incluyeron los parámetros en RVS en los modelos porque mostraron una mayor precisión para predecir CHC que las mediciones basales. Las variables asociadas de forma independientes con CHC fueron: ET (HR 1,03 IC; IC 95%, 1,01-1,05), edad (HR 1,04; IC 95%, 1,01-1,08) y niveles de albúmina (HR 0,90; IC 95%, 0,84-0,97) en el Modelo-A, y FIB-4 (HR 1,22; IC 95%, 1,08-1,37) y albúmina (HR 0,90; IC 95%, 0,84-0,97) en el Modelo-B. Ambos modelos permiten la estratificación del riesgo de CHC, identificando grupos de bajo riesgo con una tasa de incidencia de CHC de 0,16/100 y 0,25/100 PA, respectivamente. Se observó un aumento general del riesgo de desarrollar CHC con el tiempo. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hepatite C/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Estudos Prospectivos , Hepatite Crônica , Neoplasias Hepáticas , Fatores de Risco , Albuminas/uso terapêutico , Antivirais/uso terapêutico
9.
J. physiol. biochem ; 79(4): 731-743, nov. 2023.
Artigo em Inglês | IBECS | ID: ibc-227548

RESUMO

Hepatocellular carcinoma (HCC) markedly enhances liver secretion of fibroblast growth factor 21 (FGF-21), a hepatokine that increases brown and subcutaneous inguinal white adipose tissues (BAT and iWAT, respectively) uncoupling protein 1 (UCP-1) content, thermogenesis and energy expenditure. Herein, we tested the hypothesis that an enhanced BAT and iWAT UCP-1-mediated thermogenesis induced by high levels of FGF-21 is involved in HCC-associated catabolic state and fat mass reduction. For this, we evaluated body weight and composition, liver mass and morphology, serum and tissue levels of FGF-21, BAT and iWAT UCP-1 content, and thermogenic capacity in mice with Pten deletion in hepatocytes that display a well-defined progression from steatosis to steatohepatitis (NASH) and HCC upon aging. Hepatocyte Pten deficiency promoted a progressive increase in liver lipid deposition, mass, and inflammation, culminating with NASH at 24 weeks and hepatomegaly and HCC at 48 weeks of age. NASH and HCC were associated with elevated liver and serum FGF-21 content and iWAT UCP-1 expression (browning), but reduced serum insulin, leptin, and adiponectin levels and BAT UCP-1 content and expression of sympathetically regulated gene glycerol kinase (GyK), lipoprotein lipase (LPL), and fatty acid transporter protein 1 (FATP-1), which altogether resulted in an impaired whole-body thermogenic capacity in response to CL-316,243. In conclusion, FGF-21 pro-thermogenic actions in BAT are context-dependent, not occurring in NASH and HCC, and UCP-1-mediated thermogenesis is not a major energy-expending process involved in the catabolic state associated with HCC induced by Pten deletion in hepatocytes. (AU)


Assuntos
Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Hepatócitos , Termogênese/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
10.
J. physiol. biochem ; 79(4): 757-770, nov. 2023.
Artigo em Inglês | IBECS | ID: ibc-227550

RESUMO

Recent studies suggest that Rab11-family interacting proteins (Rab11-FIPs) play an important role in tumorigenesis and progression. Among the Rab11-FIPs, Rab11-FIP4 has been reported to be significantly upregulated in various cancers, including hepatocellular carcinoma (HCC). However, the possible effect on HCC stemness and the underlying mechanism has never been characterized. Here, we found that Rab11-FIP4 was dramatically increased in HCC cell lines and tissues, and had a positive correlation with cancer stemness. Functional studies revealed that elevated expression of Rab11-FIP4 in HCC cells significantly promoted sphere formation, and enhanced the mRNA and protein levels of stemness-associated markers, ALDH1A1, CD133, NANOG, and OCT4. Conversely, the knockdown of Rab11-FIP4 suppressed the cancer stem cell (CSC)-like characteristics of HCC cells. Moreover, silencing of Rab11-FIP4 obviously increased the sensitivity of HCC cells to sorafenib. Mechanistically, Rab11-FIP4 was shown to interact with ADP-ribosylation factor 5 (ARF5) to influence cell cycle-related proteins, CDK1/cyclin B, thereby promoting HCC stemness. Taken together, our results uncovered an essential role for Rab11-FIP4 in regulating CSC-like features of HCC cells and identified Rab11-FIP4 as a potential target for HCC therapy. (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fatores de Ribosilação do ADP/metabolismo , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Sorafenibe , Proteínas de Transporte/fisiologia
11.
J. physiol. biochem ; 79(4): 771-785, nov. 2023.
Artigo em Inglês | IBECS | ID: ibc-227551

RESUMO

With recent advancements in single-cell sequencing and machine learning methods, new insights into hepatocellular carcinoma (HCC) progression have been provided. Protein kinase–related genes (PKRGs) affect cell growth, differentiation, apoptosis, and signaling during HCC progression, making the predictive relevance of PKRGs in HCC highly necessary for personalized medicine. In this study, we analyzed single-cell data of HCC and used the machine learning method of LASSO regression to construct PKRG prediction models in six major cell types. CDK4 and AURKB were found to be the best PKRG prognostic signature for predicting the overall survival of HCC patients (including TCGA, ICGC, and GEO datasets) in hepatocytes. Independent clinical factors were further screened out using the COX regression method, and a nomogram combining PKRGs and cancer status was created. Treatment with Palbociclib (CDK4 Inhibitor) and Barasertib (AURKB Inhibitor) inhibited HCC cell migration. Patients classified as PKRG high- or low-risk groups showed different tumor mutation burdens, immune infiltrations, and gene enrichment. The PKRG high-risk group showed higher tumor mutation burdens and gene set enrichment analysis indicated that cell cycle, base excision repair, and RNA degradation pathways were more enriched in these patients. Additionally, the PKRG high-risk group demonstrated higher infiltration levels of Naïve CD8+ T cells, Endothelial cells, M2 macrophage, and Tregs than the low-risk group. In summary, this study established the hepatocytes-related PKRG signature for prognostic stratification at the single-cell level by using machine learning algorithms in HCC and identified potential HCC treatment targets based on the PKRG signature. (AU)


Assuntos
Humanos , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/genética , Células Endoteliais , Hepatócitos , Algoritmos
12.
J. physiol. biochem ; 79(4): 901-924, nov. 2023. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-227561

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition with a complex etiology. Its incidence is increasing globally in parallel with the obesity epidemic, and it is now considered the most common liver disease in Western countries. The precise mechanisms underlying the development and progression of NAFLD are complex and still poorly understood. The dysregulation of epigenetic and epitranscriptomic mechanisms is increasingly recognized to play pathogenic roles in multiple conditions, including chronic liver diseases. Here, we have performed a comprehensive analysis of the expression of epigenetic and epitranscriptomic genes in a total of 903 liver tissue samples corresponding to patients with normal liver, obese patients, and patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), advancing stages in NAFLD progression. We integrated ten transcriptomic datasets in an unbiased manner, enabling their robust analysis and comparison. We describe the complete landscape of epigenetic and epitranscriptomic genes’ expression along the course of the disease. We identify signatures of genes significantly dysregulated in association with disease progression, particularly with liver fibrosis development. Most of these epigenetic and epitranscriptomic effectors have not been previously described in human NAFLD, and their altered expression may have pathogenic implications. We also performed a comprehensive analysis of the expression of enzymes involved in the metabolism of the substrates and cofactors of epigenetic and epitranscriptomic effectors. This study provides novel information on NAFLD pathogenesis and may also guide the identification of drug targets to treat this condition and its progression towards hepatocellular carcinoma. (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Neoplasias Hepáticas/patologia , Epigênese Genética , Cirrose Hepática/genética , Obesidade/genética , Obesidade/metabolismo
13.
Nutr. hosp ; 40(5): 1009-1016, SEPTIEMBRE-OCTUBRE, 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-226302

RESUMO

Introduction: nutritional status and platelet-to-lymphocyte ratio (PLR) have been found to be associated with prognosis in patients with hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE).Objectives: to evaluate the association between nutritional status and PLR in patients with HCC undergoing TACE. Methods: a total of 152 HCC patients received TACE were enrolled. The nutritional status was evaluated by Patient-Generated Subjective Global Assessment (PG-SGA). Patients with PG-SGA A and PG-SGA (B or C) were classified as the well-nourished and malnourished groups. Results: according to the PG-SGA, 130 (85.5 %) patients were malnourished. The median PLR was significantly different between well-nourishedand malnourished groups (p = 0.008). A positive correlation was found between PLR and PG-SGA score (r = -0.265, p = 0.001). The optimalPLR cutoff value was 102.165 to predict malnutrition, with a sensitivity of 65.4 %, specificity of 72.7 %, and an area under the curve (AUC) of0.677 (95 % confidence interval (CI): 0.550-0.804; p = 0.008). A logistic stepwise regression model showed that the PLR was associated withnutritional status in Model 1 without adjustment, as well as if adjusted by age, sex, type of TACE (c-TACE/DEB-TACE) and Child–Pugh stage (oddsratio, 0.190; 95 % CI: 0.062-0.582; p=0.004). Conclusions: nutritional status measured by PG-SGA was significantly associated with PLR in patients with HCC undergoing TACE. (AU)


Introducción: se ha encontrado que el estado nutricional y el índice plaquetas-linfocitos (PLR) se asocian con el pronóstico en pacientes con carcinoma hepatocelular (CHC) sometidos a quimioembolización transarterial (TACE).Objetivos: evaluar la asociación entre el estado nutricional y la PLR en pacientes con CHC sometidos a TACE. Métodos: se evaluaron 152 pacientes con CHC que recibieron TACE. El estado nutricional fue evaluado por Evaluación Global Subjetiva Generada por el Paciente (PG-SGA). Los pacientes con PG-SGA A y PG-SGA (B o C) se clasificaron como los grupos bien nutridos y desnutridos. Resultados: según la PG-SGA, 130 (85,5 %) pacientes estaban desnutridos. La mediana de PLR fue significativamente diferente entre los grupos bien nutridos y desnutridos (p = 0,008). Se encontró una correlación positiva entre PLR y la puntuación PG-SGA (r = -0,265, p = 0,001). El valor de corte óptimo de PLR fue de 102,165 para predecir la malnutrición, con una sensibilidad del 65,4 %, una especificidad del 72,7 % y un área bajo la curva (AUC) de 0,677 (intervalo de confianza [IC] del 95 %: 0,550-0,804; p = 0,008). Un modelo de regresión logística escalonada mostró que el PLR se asoció con el estado nutricional en el Modelo 1 sin ajuste, así como cuando se ajustó por edad, sexo, tipo de TACE (c-TACE/DEB-TACE) y etapa Child-Pugh (odds ratio, 0,190; IC 95 %: 0,062-0,582; p = 0,004).Conclusiones: el estado nutricional medido por PG-SGA se asoció significativamente con PLR en pacientes con CHC sometidos a TACE. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Estado Nutricional , Plaquetas , Linfócitos
15.
Clin. transl. oncol. (Print) ; 25(10): 2960-2971, oct. 2023. graf
Artigo em Inglês | IBECS | ID: ibc-225077

RESUMO

Objective Downregulation of miR-17-5p has been reported in several cancers, but whether and how miR-17-5p is downregulated in hepatocellular carcinoma (HCC) is unknown. Here, we examined whether miR-17-5p is downregulated in HCC and whether that affects expression of its target gene encoding transforming growth factor β receptor 2 (TGFβR). Methods We screened for potential microRNAs (miRNAs) involved in HCC by analyzing published transcriptomes from HCC patients. Expression of miR-17-5p was measured in HCC cell lines and in tissues from HCC patients using quantitative real-time PCR. The in vitro effects of miR-17-5p on HCC cells were assessed by EdU proliferation assay, CCK-8 cell proliferation assay, colony-formation assay, transwell migration/invasion assay, wound healing assay, and flow cytometry. Effects of miR-17-5p were evaluated in vivo using mice with subcutaneous tumors. Effects of the miRNA on the epithelial–mesenchymal transition (EMT) were assessed, while its effects on TGFβR2 expression were analyzed using bioinformatics and a dual luciferase reporter assay. Results Patients with low miR-17-5p expression showed lower rates of overall and recurrence-free survival than patients with high miR-17-5p expression, and multivariate Cox regression identified low miR-17-5p expression as an independent predictor of poor overall survival in HCC patients. In vitro, miR-17-5p significantly inhibited HCC cell proliferation, migration, invasion, and the EMT, while promoting apoptosis. In vivo, it slowed the development of tumors. These protective effects of miR-17-5p were associated with downregulation of TGFβR2. Conclusion The miRNA miR-17-5p can negatively regulate the expression of TGFβR2 and inhibit the EMT, thereby slowing tumor growth in HCC, suggesting a potential therapeutic approach against HCC (AU)


Assuntos
Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
16.
Clin. transl. oncol. (Print) ; 25(8): 2499-2513, aug. 2023. graf
Artigo em Inglês | IBECS | ID: ibc-222426

RESUMO

Purpose The de novo lipogenesis has been a longstanding observation in hepatocellular carcinoma (HCC). However, the prognostic value and carcinogenic roles of the enzyme Acetyl-CoA carboxylase alpha (ACACA) in HCC remains unknown. Methods The proteins with remarkable prognostic significance were screened out from The Cancer Proteome Atlas Portal (TCPA) database. Furthermore, the expression characteristics and prognostic value of ACACA were evaluated in multiple databases and the local HCC cohort. The loss-of-function assays were performed to uncover the potential roles of ACACA in steering malignant behaviors of HCC cells. The underlying mechanisms were conjectured by bioinformatics and validated in HCC cell lines. Results ACACA was identified as a crucial factor of HCC prognosis. Bioinformatics analyses showed that HCC patients with higher expression of ACACA protein or mRNA levels had poor prognosis. Knockdown of ACACA remarkably crippled the proliferation, colony formation, migration, invasion, epithelial−mesenchymal transition (EMT) process of HCC cells and induced the cell cycle arrest. Mechanistically, ACACA might facilitate the malignant phenotypes of HCC through aberrant activation of Wnt/β-catenin signaling pathway. In addition, ACACA expression was associated with the dilute infiltration of immune cells including plasmacytoid DC (pDC) and cytotoxic cells by utilization of relevant database analysis. Conclusion ACACA could be a potential biomarker and molecular target for HCC (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , beta Catenina/metabolismo , Prognóstico
17.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 42(4): 255-264, jul.- ago. 2023. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-223282

RESUMO

Objetivo Para conocer los resultados de la radioembolización (transarterial radioembolization o TARE), en el tratamiento de tumores hepáticos, se realizó una valoración retrospectiva tras 112 TARE con 90Y-microesferas administradas en 82 pacientes en un único hospital, analizando la eficacia y la seguridad, tras un seguimiento mayor o igual a 1 año post-TARE en todos los pacientes, y evaluando la posible relación entre la respuesta al tratamiento y la supervivencia de los pacientes. Material y métodos Se administraron 57 TARE únicas y 55 TARE múltiples en pacientes con hepatocarcinoma (53), metástasis hepáticas (25) y colangiocarcinoma (4), con evaluación previa multidisciplinar clínica, angiográfica y gammagráfica (planar/SPECT/SPECT-TC con 99mTc-MAA), modelo multicompartimental (ecuaciones MIRD), valoración gammagráfica post-TARE (planar/SPECT/SPECT-TC), seguimiento clínico-radiológico, evaluación de respuesta tumoral (criterios mRECIST) y análisis (Kaplan Meier) de supervivencia libre de progresión (SLP) y supervivencia global (SG). Resultados La intención terapéutica fue paliativa (82%) y como puente a trasplante hepático/resección quirúrgica (17%). Se obtuvo respuesta (R), completa o parcial, en el 65,9% de los casos. Al año post-TARE estaban libres de progresión el 34,7% de los pacientes con R y 19,2% de los no R (p:0,003), con SG del 80% para los R y 37,5% para los no R (p:0,001). Las curvas de supervivencia mostraron mediana de SG de 18 meses (95% IC 15,7-20,3) para los R y 9 meses (95% IC 6,1-11,8) para los no R (p:0,03). Efectos secundarios leves (27,6%) y severos (5,3%) resueltos, sin mayor incidencia tras TARE múltiple. Conclusiones La TARE con 90Y-microesferas en pacientes adecuadamente seleccionados con tumores hepáticos, aporta eficacia terapéutica y bajo índice de toxicidad, con SLP y SG superiores en los pacientes con respuesta a la TARE respecto a los que no respondieron (AU)


Aim To determine the results of radioembolization transarterial (TARE), in the treatment of liver tumors, a retrospective evaluation was performed after 112 TARE with 90Y-microspheres administered in 82 patients in a single hospital, analyzing efficacy and safety, after a follow-up greater than or equal to 1 year post-TARE in all patients, and evaluating the possible relationship between treatment response and patient survival Material and methods We have administered 57 single TARE and 55 multiple TARE in patients with hepatocellular carcinoma (53), liver metastases (25) and cholangiocarcinoma (4), with prior multidisciplinary evaluation, clinical, angiographic and gammagraphic (planar/SPECT/SPECT-CT with 99mTc-MAA), multicompartment model (MIRD equations), post-TARE screening (planar/SPECT/SPECT-CT), clinical and radiological follow-up, tumor response evaluation (mRECIST criteria) and Kaplan–Meier analysis to determine progression-free survival (PFS) and overall survival (OS). Results Therapeutic intention was palliative (82%) and as bridge to liver transplantation/surgical resection (17%). We obtained response (R), complete or partial, in 65.9% of cases. One year after TARE 34.7% of patients with R and 19.2% of non-R were progression-free (p: 0.003), with OS of 80% for R and 37.5% for non-R (p: 0.001). Survival analysis showed median OS of 18 months (95% CI 15.7–20.3) for R and 9 months (95% CI 6.1–11.8) for non-R (p: 0.03). We found mild (27.6%) and severe (5.3%) side effects, all of them resolved, without higher incidence after multiple TARE. Conclusion TARE with 90Y-microspheres, in appropriately selected patients with liver tumors, provides therapeutic efficacy and low rate of toxicity, with higher PFS and OS in patients with TARE response compared to those who did not respond (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Embolização Terapêutica , Microesferas , Radioisótopos de Ítrio , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Colangiocarcinoma/terapia , Resultado do Tratamento , Radiografia Intervencionista , Metástase Neoplásica , Análise de Sobrevida
18.
J. physiol. biochem ; 79(3): 669-682, ago. 2023.
Artigo em Inglês | IBECS | ID: ibc-223756

RESUMO

Current evidence finds that circulating exosomal lncRNA focally amplified lncRNA on chromosome 1 (FAL1) promotes the progression of hepatocellular carcinoma (HCC). However, the underlying mechanism of serum extracellular vesicular FAL1 in HCC progression remains elusive. Here, we extracted extracellular vesicles (EVs) from serum samples of HCC patients and healthy volunteers, and found that FAL1 was highly enriched in the serum EVs of HCC patients. Then, macrophages were treated with EVs alone or together with small interfering RNA against FAL1 (si-FAL1). The data indicated that FAL1-enriched EVs induced macrophage M2 polarization, while silencing FAL1 in macrophages antagonized the role of EVs. Moreover, HepG2 cells were co-cultured with the conditioned macrophages, and co-culturing with EVs-incubated macrophages promoted HepG2 cell proliferation, invasion, cell cycle progression, and colony formation, and inhibited cell apoptosis and sorafenib sensitivity, while interfering FAL1 in macrophages reversed these effects. Consistently, ectopic expression of FAL1 in macrophages also induced macrophage M2 polarization, and co-culture of FAL1-overexpressing macrophages with HepG2 cells facilitated the malignant progression of HepG2 cells. Furthermore, co-culturing HepG2 cells with EVs-incubated macrophages activated the Wnt/β-catenin signaling pathway, and treatment with a Wnt/β-catenin pathway inhibitor IWP-2 partially neutralized the effect of EVs-incubated macrophages on HepG2 cell malignant behaviors. Additionally, FAL1 enriched EVs-incubated macrophages markedly increased mouse xenograft tumor growth. In conclusion, extracellular vesicular lncRNA FAL1 promotes macrophage M2 polarization and further activates the Wnt/β-catenin signaling pathway in HCC cells, thus promoting HCC progression. (AU)


Assuntos
Humanos , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Macrófagos/metabolismo , Proliferação de Células , Linhagem Celular Tumoral
19.
Clin. transl. oncol. (Print) ; 25(7): 2099-2115, jul. 2023. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-222381

RESUMO

Purpose Hepatocellular carcinoma (HCC) is a highly vascularized tumor, and angiogenesis plays an important role in its progression. However, the role of angiogenesis in cell infiltration in the tumor microenvironment (TME) remains unclear. Methods We evaluated the associations of 35 angiogenesis-related genes (ARGs) with the clinicopathological features of 816 HCC patients. In addition, we assessed the associations between the ARGs and TME cell infiltration. A nomogram was constructed to determine the prognostic value of ARGs for HCC. The ARG score was used to distinguish angiogenic subtypes of HCC, and its usefulness for predicting the prognosis and treatment response of HCC patients was evaluated. Results We distinguished three ARG clusters differing in terms of TME cell infiltration, immune cell activation status, clinicopathological features, and clinical outcomes. There were significant associations of ARG expression with tumor immunity, the epithelial–mesenchymal transition (EMT), and transforming growth factor-β expression. An ARG score model was constructed to generate a risk score for each patient based on differentially expressed genes between clusters. Furthermore, a high ARG score was associated with high expression of CTLA-4 and PD-L1/PD-1, and a low Tumor Immune Dysfunction and Exclusion score, indicating the usefulness of the ARG score for selecting patients for immunotherapy. Considering the relationship between ARGs and tumor immunity, immunotherapy combined with vascular-targeted therapy may be the best treatment for HCC. Conclusions ARGs play an important role in TME diversity and complexity in HCC patients. The ARG score of HCC predicts TME invasion and can guide immunotherapy (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Transição Epitelial-Mesenquimal , Microambiente Tumoral , Imunoterapia , Prognóstico
20.
Clin. transl. oncol. (Print) ; 25(7): 2224-2238, jul. 2023. ilus
Artigo em Inglês | IBECS | ID: ibc-222390

RESUMO

Purpose Dishevelled-associated activator of morphogenesis 2 (DAAM2) is a formin protein and has a potential role in the tumor metastasis. The prognostic value of DAAM2 in pan-cancer is investigated in this study. Methods TCGA and GTEx database were downloaded to perform bioinformatics analysis and ROC curves. Then we explored protein–protein interaction and GO-KEGG enrichment to figure out the protein pathways associated with DAAM2 and studied DAAM2-related immune infiltration and methylation. Fifteen pairs of BRCA clinical samples were enrolled to determine the expression and distribution of DAAM2 in BRCA sections by immunohistochemistry. Finally, BRCA cells were transfected with siRNA targeting DAAM2 and subsequently subject to cell proliferation, migration, and invasion assays. Results DAAM2 was closely related to the diagnosis and clinical characteristics of lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and breast cancer (BRCA). Survival curve analysis demonstrated DAAM2 served as a potential prognostic indicator of LGG and LIHC (P = 0.0029 and P = 0.025, respectively). DAAM2 was mainly participated in signaling pathways mediating cytoskeleton regulation and tumor development. The correlation of DAAM2 with tumor-infiltrating immune cells (TIICs) and methylation levels was conducive to the prediction of novel biomarkers of pan-carcinoma. DAAM2 was highly expressed in BRCA tissues than that in paracancerous tissues. The proliferation, invasion, and migration of BRCA cells were inhibited by DAAM2 siRNA. Conclusion DAAM2 had a specific value in foretelling the prognosis of LGG, LIHC, and BRCA. High expression level of DAAM2 has longer survival rates in LGG and LIHC. The knockdown of DAAM2 retards the proliferation, invasion, and migration of BRCA cells. This study provides a novel sight of DAAM2 into the exploration of a potential biomarker in pan-cancer (AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/genética , Carcinoma Hepatocelular/genética , Glioma/genética , Neoplasias Hepáticas/genética , Proteínas dos Microfilamentos , Morfogênese , Prognóstico , Proteínas rho de Ligação ao GTP
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