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1.
Anticancer Res ; 41(4): 1975-1983, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813404

RESUMEN

BACKGROUND/AIM: Few studies have established a definite conclusion regarding the limitation of surgical treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B and C hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A retrospective analysis was performed on 717 consecutive patients who underwent initial hepatectomy for HCC. RESULTS: Reductive hepatectomy was performed in 103 patients, with a median survival time (MST) of 18.0 months. Total bilirubin and albumin levels were identified as independent prognostic factors. The predictive score of these factors ranged from 0 to 2. Subsequent local treatment was performed in 91.0, 75.0, and 25.0% of patients who scored 0, 1, and 2, respectively. The MST for patients with a score of 0, 1, and 2 was 20.1, 14.8, and 2.7 months, respectively, with a significant difference. CONCLUSION: Patients with BCLC stage B and C could be properly treated with reductive hepatectomy and subsequent local treatments.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Procedimientos Quirúrgicos de Citorreducción , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Procedimientos Quirúrgicos de Citorreducción/métodos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Hepatectomía/efectos adversos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/etiología , Neoplasia Residual/mortalidad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
2.
Medicine (Baltimore) ; 100(17): e25640, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33907121

RESUMEN

ABSTRACT: Programmed death protein 1 (PD-1) pathway is one of the most critical mechanisms in tumor biology of hepatocellular carcinoma (HCC). The study aimed to assess the prognostic influence of pretransplant serum soluble PD-1 (sPD-1) in patients undergoing liver transplantation for treatment of HCC.Data from 229 patients with HCC who underwent living donor liver transplantation between January 2010 and December 2015 were retrospectively evaluated. Stored serum samples were used to measure sPD-1 concentrations.Overall survival (OS) and disease-free survival (DFS) rates were 94.3% and 74.5% at 1 year; 78.2% and 59.2% at 3 years; and 75.4% and 55.5% at 5 years, respectively. Prognostic analysis using pretransplant serum sPD-1 with a cut-off of 93.6 µg/mL (median value of the study cohort) did not have significant prognostic influence on OS (P = .69) and DFS (P = .26). Prognostic analysis using sPD-1 with a cut-off of 300 µg/mL showed similar OS (P = .46) and marginally lower DFS (P = .070). Combination of Milan criteria and sPD-1 with a cutoff of 300 µg/mL showed similar outcomes of OS and DFS in patients within and beyond Milan criteria. Multivariate analysis revealed that only Milan criteria was an independent prognostic for OS and DFS, but pretransplant sPD1 with a cut-off of 300 µg/mL did not become a prognostic factor.The results of this study demonstrate that pretransplant serum sPD-1 did not show significant influences on post-transplant outcomes in patients with HCC. Further large-scale, multicenter studies are necessary to clarify the role of serum sPD-1 in liver transplantation recipients.


Asunto(s)
Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , Trasplante de Hígado/mortalidad , Receptor de Muerte Celular Programada 1/sangre , Adulto , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Donadores Vivos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Resultado del Tratamiento
3.
Anticancer Res ; 41(3): 1563-1570, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788750

RESUMEN

BACKGROUND/AIM: This study aimed to evaluate how NAD(P)H: quinone oxidoreductase-1 (NQO1) affects survival after hepatectomy in patients with colorectal liver metastasis (CRLM). PATIENTS AND METHODS: A retrospective analysis was conducted of 88 consecutive patients who underwent hepatectomy for CRLM. Of the 88 patients, preoperative chemotherapy was administered to 30 patients. Immunohistochemistry of the resected specimens was conducted using monoclonal anti-NQO1 antibody. RESULTS: NQO1-positive expression in tumor cells of CRLM was associated with worse overall survival (p=0.026) and was an independent adverse prognostic factor in multivariate analysis (hazard ratio=5.296, p=0.007). Among 30 patients who received preoperative chemotherapy, patients with loss of NQO1 expression in non-neoplastic epithelial cells of the bile ducts (NQO1 polymorphism: n=19) showed significantly better response to preoperative chemotherapy for CRLM (p=0.004). CONCLUSION: NQO1-positive expression in tumor cells of CRLM may be an adverse prognostic factor after hepatectomy for CRLM.


Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , NAD(P)H Deshidrogenasa (Quinona)/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , NAD(P)H Deshidrogenasa (Quinona)/genética , Polimorfismo Genético , Pronóstico
4.
Medicine (Baltimore) ; 100(12): e25234, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761715

RESUMEN

ABSTRACT: This study investigated the expression change, prognostic values, and potential regulatory mechanisms of mortality factor on chromosome 4 (MORF4)-related gene-binding protein (MRGBP) in hepatocellular carcinoma (HCC).MRGBP expression and clinical data from The Cancer Genome Atlas were used to evaluate the associations between MRGBP expression and clinicopathological characteristics. Kaplan-Meier and Cox regression analyses were performed to assess the factors contributing to prognosis. Gene set enrichment analysis (GSEA) was used to identify pathways associated with MRGBP expression. Single-sample gene set enrichment analysis (ssGSEA) was used to comprehensively analyze the relative immune infiltration levels.High MRGBP expression was significantly associated with a higher T stage, pathologic stage, histologic grade, vascular invasion, tumor protein p53 status, and worse overall survival. MRGBP exhibited high diagnostic accuracy with an area under the receiver operating characteristic curve value of 0.980. GSEA revealed the enrichment of pathways related to tumorigenesis in the MRGBP high-expression phenotype, such as cell cycle and DNA replication pathways. ssGSEA revealed that MRGBP expression was significantly correlated with 15 types of immune cell infiltration levels. The Wilcoxon rank sum test revealed significantly high T helper (Th), T follicular helper, CD56 bright natural killer, and Th2 cell enrichment scores in the high MRGBP expression group and significantly low neutrophil, Th17, dendritic cell (DC), gamma delta T, cytotoxic cell, regulatory T cell, plasmacytoid DC, and immature DC enrichment scores.MRGBP may be a novel prognostic biomarker and a therapeutic target correlated with immune infiltrates in HCC.


Asunto(s)
Carcinoma Hepatocelular , Histona Acetiltransferasas , Neoplasias Hepáticas , Hígado , Proteínas Nucleares , Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Biología Computacional/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Histona Acetiltransferasas/análisis , Histona Acetiltransferasas/genética , Humanos , Estimación de Kaplan-Meier , Hígado/inmunología , Hígado/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Proteínas Nucleares/análisis , Proteínas Nucleares/genética , Pronóstico
5.
Medicine (Baltimore) ; 100(11): e24476, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725934

RESUMEN

ABSTRACT: The platelet-albumin-bilirubin (PALBI) grade plays critical role in evaluating liver function. However, the change of PALBI grade from the preoperative to postoperative period in predicting patient outcomes after hepatectomy remains unclear.A total of 489 HCC patients who underwent hepatectomy in West China Hospital between January, 2010 and June, 2016 were analyzed retrospectively.ΔPALBI grade was calculated by PALBI grade at the first postoperative month - preoperative PALBI grade.ΔPALBI >0 was considered as stable; otherwise, worse PALBI grade was considered. Kaplan- Meier method and Cox proportional hazard regression analyses were performed for survival analysis. Prognostic model was constructed by nomogram method.Three hundred forty two patients and 147 patients were classified into training group and validation group, respectively. In the training group, results from Cox model suggested that worse PALBI grade (HR 1.328, 95% CI 1.010-1.746, P = .042), tumor size (HR 1.460, 95% CI 1.058-2.015, P = .021), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P < .001), and high alpha-fetoprotein level (AFP, HR 1.364, 95% CI 1.044-1.781, P = .023) negatively influenced postoperative recurrence. Similarly, worse PALBI grade (HR 1.403, 95% CI 1.020-1.930, P = .038), tumor size (HR 1.708, 95% CI 1.157-2.520, P = .007), MVI (HR 1.914, 95% CI 1.375-2.663, P < .001), and presence of cirrhosis (HR 1.773, 95% CI 1.226-2.564, P = .002) had negatively impacts on overall survival. Patients with worse PALBI grade had worse recurrence free (RFS) and overall survival (OS). The prognostic model incorporating the change of PALBI grade constructed in training group and tested in the validation group could perform well in predicting the outcomes.Postoperative change of PALBI grade was independently risk factor related with prognosis. Prognostic model incorporating the change of PALBI grade might be a useful index to predict the prognosis of HCC patients following hepatectomy.


Asunto(s)
Bilirrubina/sangre , Carcinoma Hepatocelular/sangre , Hepatectomía/mortalidad , Pruebas de Función Hepática/métodos , Neoplasias Hepáticas/sangre , Recuento de Plaquetas , Albúmina Sérica/análisis , Adulto , Anciano , Biomarcadores de Tumor , Plaquetas , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Cirrosis Hepática/mortalidad , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Nomogramas , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
6.
Br J Surg ; 108(2): 196-204, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33711132

RESUMEN

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía , Laparoscopía , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Femenino , Hepatectomía/efectos adversos , Hepatectomía/métodos , Hepatectomía/mortalidad , Humanos , Hipertensión Portal/patología , Laparoscopía/efectos adversos , Laparoscopía/métodos , Laparoscopía/mortalidad , Tiempo de Internación/estadística & datos numéricos , Cirrosis Hepática/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Adulto Joven
7.
BMC Cancer ; 21(1): 250, 2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33685409

RESUMEN

BACKGROUND: We quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment. METHODS: Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. RESULTS: One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence (< 1 year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (> 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI:1.01-2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26-3.08), early recurrence (HR = 6.62, 95% CI:3.79-11.6) and late recurrence (HR = 3.75, 95% CI:1.99-7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE. CONCLUSION: Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/estadística & datos numéricos , Hepatectomía/estadística & datos numéricos , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia/epidemiología , Ablación por Radiofrecuencia/estadística & datos numéricos , Anciano , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Factores de Tiempo
8.
BMC Cancer ; 21(1): 246, 2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33685417

RESUMEN

BACKGROUND: Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. METHODS: A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. RESULTS: The C-index of nomogram1was 0.708 (95%CI: 0.673-0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606-0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690-0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691-0.813; AUC: 0.784, 95%CI: 0.709-0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. CONCLUSIONS: Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/mortalidad , Nomogramas , alfa-Fetoproteínas/análisis , Biopsia , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Hígado/diagnóstico por imagen , Hígado/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
9.
BMC Cancer ; 21(1): 283, 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33726693

RESUMEN

BACKGROUND: The accurate prediction of post-hepatectomy early recurrence (PHER) of hepatocellular carcinoma (HCC) is vital in determining postoperative adjuvant treatment and monitoring. This study aimed to develop and validate an artificial neural network (ANN) model to predict PHER in HCC patients without macroscopic vascular invasion. METHODS: Nine hundred and three patients who underwent curative liver resection for HCC participated in this study. They were randomly divided into derivation (n = 679) and validation (n = 224) cohorts. The ANN model was developed in the derivation cohort and subsequently verified in the validation cohort. RESULTS: PHER morbidity in the derivation and validation cohorts was 34.8 and 39.2%, respectively. A multivariable analysis revealed that hepatitis B virus deoxyribonucleic acid load, γ-glutamyl transpeptidase level, α-fetoprotein level, tumor size, tumor differentiation, microvascular invasion, satellite nodules, and blood loss were significantly associated with PHER. These factors were incorporated into an ANN model, which displayed greater discriminatory abilities than a Cox's proportional hazards model, preexisting recurrence models, and commonly used staging systems for predicting PHER. The recurrence-free survival curves were significantly different between patients that had been stratified into two risk groups. CONCLUSION: When compared to other models and staging systems, the ANN model has a significant advantage in predicting PHER for HCC patients without macroscopic vascular invasion.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/epidemiología , Redes Neurales de la Computación , Nomogramas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Hepatectomía , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo
10.
BMC Cancer ; 21(1): 278, 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33726698

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. We aimed to identify a new prognostic model of HCC based on differentially expressed (DE) immune genes. METHODS: The DE immune genes were identified based on an analysis of 374 cases of HCC and 50 adjacent non-tumor specimens from the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, Lasso regression, and multivariate Cox analysis were used to construct the model based on the training group. Survival analysis and the receiver operating characteristic (ROC) curves were used to evaluate model performance. The testing group and the entire group were subsequently used for validation of the model. RESULTS: A five-immune gene model consisted of HSPA4, ISG20L2, NDRG1, EGF, and IL17D was identified. Based on the model, the overall survival was significantly different between the high-risk and low-risk groups (P = 7.953e-06). The AUCs for the model at 1- and 3-year were 0.849 and 0.74, respectively. The reliability of the model was confirmed using the validation groups. The risk score was identified as an independent prognostic parameter and closely related to the content of immune cells from human HCC specimens. CONCLUSION: We identified a five-immune gene model that can be used as an independent prognostic marker for HCC.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/mortalidad , Regulación Neoplásica de la Expresión Génica/inmunología , Neoplasias Hepáticas/mortalidad , Modelos Genéticos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Biología Computacional , Conjuntos de Datos como Asunto , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Hígado/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
11.
BMC Cancer ; 21(1): 280, 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33726700

RESUMEN

BACKGROUND: Although criteria for liver transplantation, such as the Milan criteria and Hangzhou experiences, have become popular, criteria to guide adjuvant therapy for patients with hepatocellular carcinoma after liver transplantation are lacking. METHODS: We collected data from all consecutive patients from 2012 to 2019 at three liver transplantation centers in China retrospectively. Univariate and multivariate analyses were used to analyze preoperative parameters, such as demographic and clinical data. Using data obtained in our center, calibration curves and the concordance Harrell's C-indices were used to establish the final model. The validation cohort comprised the patients from the other centers. RESULTS: Data from 233 patients were used to construct the nomogram. The validation cohort comprised 36 patients. Independent predictors of overall survival (OS) were identified as HbeAg positive (P = 0.044), blood-type compatibility unmatched (P = 0.034), liver transplantation criteria (P = 0.003), and high MELD score (P = 0.037). For the validation cohort, to predict OS, the C-index of the nomogram was 0.874. Based on the model, patients could be assigned into low-risk (≥ 50%), intermediate-risk (30-50%), and high-risk (≤ 30%) groups to guide adjuvant therapy after surgery and to facilitate personalized management. CONCLUSIONS: The OS in patients with hepatocellular carcinoma after liver transplantation could be accurately predicted using the developed nomogram.


Asunto(s)
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Trasplante de Hígado/efectos adversos , Nomogramas , Complicaciones Posoperatorias/epidemiología , Adulto , Carcinoma Hepatocelular/mortalidad , Quimioterapia Adyuvante , China/epidemiología , Toma de Decisiones Clínicas , Técnicas de Apoyo para la Decisión , Femenino , Mortalidad Hospitalaria , Humanos , Estimación de Kaplan-Meier , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Periodo Preoperatorio , Radioterapia Ayuvante , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo
12.
BMC Cancer ; 21(1): 307, 2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33761907

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary invasive cancer of the liver. During the last decade, the epidemiology of HCC has been continuously changing in developed countries, due to more effective primary prevention and to successful treatment of virus-related liver diseases. The study aims to examine survival by level of access to care in patients with HCC, for all patients combined and by age. METHODS: We included 2018 adult patients (15-99 years) diagnosed with a primary liver tumour, registered in the Palermo Province Cancer Registry during 2006-2015, and followed-up to 30 October 2019. We obtained a proxy measure of access to care by linking each record to the Hospital Discharge Records and the Ambulatory Discharge Records. We estimated net survival up to 5 years after diagnosis by access to care ("easy access to care" versus "poor access to care"), using the Pohar-Perme estimator. Estimates were age-standardised using International Cancer Survival Standard (ICSS) weights. We also examined survival by access to care and age (15-64, 65-74 and ≥ 75 years). RESULTS: Among the 2018 patients, 62.4% were morphologically verified and 37.6% clinically diagnosed. Morphologically verified tumours were more frequent in patients aged 65-74 years (41.6%), while tumours diagnosed clinically were more frequent in patients aged 75 years or over (50.2%). During 2006-2015, age-standardised net survival was higher among HCC patients with "easy access to care" than in those with "poor access to care" (68% vs. 48% at 1 year, 29% vs. 11% at 5 years; p < 0.0001). Net survival up to 5 years was higher for patients with "easy access to care" in each age group (p < 0.0001). Moreover, survival increased slightly for patients with easier access to care, while it remained relatively stable for patients with poor access to care. CONCLUSIONS: During 2006-2015, 5-year survival was higher for HCC patients with easier access to care, probably reflecting progressive improvement in the effectiveness of health care services offered to these patients. Our linkage algorithm could provide valuable evidence to support healthcare decision-making in the context of the evolving epidemiology of hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Neoplasias Hepáticas/mortalidad , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/terapia , Toma de Decisiones en la Organización , Técnicas de Apoyo para la Decisión , Femenino , Estudios de Seguimiento , Accesibilidad a los Servicios de Salud/organización & administración , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Humanos , Italia/epidemiología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Sistema de Registros/estadística & datos numéricos , Análisis de Supervivencia , Adulto Joven
14.
J Surg Oncol ; 123(5): 1263-1273, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33524184

RESUMEN

BACKGROUND: The association between the imaging response (structural or metabolic) to neoadjuvant chemotherapy (neoCT) before colorectal liver metastasis (CRLM) and survival is unclear. METHOD: A total of 201 patients underwent their first CRLM resection. A total of 94 (47%) patients were treated with neoCT. A multivariable, Cox proportional hazard regression analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between response groups. RESULTS: Multivariable regression analysis of the CT/MRI (n = 94) group showed no difference in survival (OS and PFS) in patients who had stable disease/partial response (SD/PR) or complete response (CR) versus patients who had progressive disease (PD) (OS: HR, 0.36 (95% CI: 0.11-1.19) p = .094, HR, 0.78 (95% CI: 0.13-4.50) p = .780, respectively), (PFS: HR, 0.70 (95% CI: 0.36-1.35) p = .284, HR, 0.51 (0.18-1.45) p = .203, respectively). In the FDG-PET group (n = 60) there was no difference in the hazard of death for patients with SD/PR or CR versus patients with PD for OS or PFS except for the PFS in the small CR subgroup (OS: HR, 0.75 (95% CI: 0.11-4.88) p = .759, HR, 1.21 (95% CI: 0.15-9.43) p = .857), (PFS: HR, 0.34% (95% CI: 0.09-1.22), p = .097, HR, 0.17 (95% CI: 0.04-0.62) p = .008, respectively). CONCLUSION: There was no convincing evidence of association between imaging response to neoCT and survival following CRLM resection.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/mortalidad , Neoplasias Colorrectales/mortalidad , Neoplasias Hepáticas/mortalidad , Terapia Neoadyuvante/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Tomografía de Emisión de Positrones/métodos , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
15.
Gene ; 779: 145493, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33588034

RESUMEN

Liver cancer is a malignant disease and causes thousands of death each year. The prognosis is dismal for patients with metastasis and recurrence. It is urgent to disclose the cause and mechanism underlying liver cancer. LARGE1 encodes a glycosyltransferase and was reported to promote progression in cancer. But its role in liver cancer is unknown. In this study, LARGE1 displayed upregulated expression in liver cancer cells. When LARGE1 was knocked down in SMMC-7721 and Huh-7 cells, the ability of cell proliferation and colony formation were decreased significantly. Cell migration and invasion were suppressed. The number of cells in G1 phase increased but decreased in S phase. Cell apoptosis was not affected. Tumor growth in vivo was also inhibited. Tumor volume was decreased from 1270 mm3 to 721 mm3 (p < 0.05) and tumor weight from 0.95 g to 0.63 g (p < 0.05). Furthermore, the expression of ß-catenin, TCF and Cyclin D1 was reduced when LARGE1 was knocked down but increased in LARGE1-overexpressed cells. LGK-974, a specific inhibitor in canonical Wnt signaling, inhibited cell proliferation even when LARGE1 was over-expressed. In tumor tissues, LARGE1 was increased by 4.8 folds compared to paratumoral tissues. And higher LARGE1 expression caused shorter survival. Clinicopathological analysis demonstrated that LARGE1 was associated with TNM stage (Ⅰ/Ⅱ vs III/IV, p = 0.005). Therefore, LARGE1 promotes progression and regulates Wnt/ß-catenin signaling pathway in liver cancer.


Asunto(s)
Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , N-Acetilglucosaminiltransferasas/genética , Animales , Apoptosis/genética , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Masculino , Ratones Desnudos , Persona de Mediana Edad , Vía de Señalización Wnt/genética , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Medicine (Baltimore) ; 100(4): e24326, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530224

RESUMEN

ABSTRACT: The spleen plays an important role in tumor progression and the curative effects of splenectomy before hepatectomy for hypersplenism and hepatocellular carcinoma (HCC) are not clear. We investigated whether splenectomy before hepatectomy increases survival rate among patients with HCC and hypersplenism compared with that of patients who underwent synchronous hepatectomy and splenectomy or hepatectomy alone.Between January 2011 and December 2016, 266 patients who underwent hepatectomy as a result of HCC and portal hypertension secondary to hepatitis were retrospectively analyzed. Their perioperative complications and survival outcome were evaluated.Patients underwent synchronous hepatectomy and splenectomy (H-S group) and underwent splenectomy before hepatectomy (H-preS group) exhibited significantly higher disease-free survival (DFS) rates than those of patients underwent hepatectomy alone (H-O group). The DFS rates for patients in the H-S group, H-preS group, and H-O group were 74.6%, 48.4%, 39.8%, and 80.1%, 54.2%, 40.1%, and 60.5%, 30.3%, 13.3%, at 1, 3, and 5 years after surgery, respectively. Tumor size, tumors number, and levels of alpha fetoprotein (AFP) were independent risk factors for DFS. Gender and tumor size were independent prognostic factor for overall survival (OS). The preoperative white blood cell (WBC) and platelet (PLT) counts were significantly higher in the H-preS group than in those of the H-S group and the H-O group. After operation, the WBC and PLT counts in the H-S group and H-preS groups were significantly higher compared to those of the H-O group.No matter splenectomy before hepatectomy or synchronous hepatectomy and splenectomy, hepatectomy with splenectomy may improve DFS rates in patients with HCC and hypersplenism, and splenectomy before hepatectomy alleviates hypersplenism without an increased surgical risk.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/mortalidad , Hiperesplenismo/cirugía , Neoplasias Hepáticas/cirugía , Esplenectomía/mortalidad , Adulto , Biomarcadores/sangre , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Hepatectomía/métodos , Humanos , Hiperesplenismo/complicaciones , Hiperesplenismo/mortalidad , Recuento de Leucocitos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Pronóstico , Estudios Retrospectivos , Esplenectomía/métodos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , alfa-Fetoproteínas/análisis
17.
Medicine (Baltimore) ; 100(4): e24354, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530229

RESUMEN

ABSTRACT: Diabetes mellitus (DM) increases the risk of developing hepatocellular carcinoma (HCC), and how DM affects the prognosis of HCC have not been elucidated. The aim of this study was to compare clinicopathological characteristics and survival between hepatitis B virus (HBV)-related HCC patients with and without DM and to determine risk factors for overall survival after hepatectomy.Among 474 patients with HBV-related HCC, 119 patients had DM. Patients were divided into the diabetic group and nondiabetic group. The short-term and long-term outcomes were evaluated by using propensity score matching analysis.After 1:2 propensity score matching, there were 107 patients in diabetic group, 214 patients in nondiabetic group. The proportion of vessels invasion were higher in diabetic group. The overall survival rate in the diabetic group was 44.7% at 3 years, which was lower than that in the nondiabetic group (56.1%, P = .025). The multivariate analysis indicated that fasting blood glucose >7.0, capsular invasion, microvascular invasion and satellite were independent risk factor of poor prognosis in HCC.DM dose affect the recurrence-free survival and overall survival in HBV-related HCC patients after hepatectomy. One of the more significant findings to emerge from this study is that DM induced higher proportion of major vessel invasion in HCC patients implied unfavorable prognosis.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Diabetes Mellitus Tipo 2/virología , Virus de la Hepatitis B , Hepatitis B/complicaciones , Neoplasias Hepáticas/mortalidad , Glucemia/análisis , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/virología , Diabetes Mellitus Tipo 2/sangre , Femenino , Hepatectomía/mortalidad , Hepatitis B/virología , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Puntaje de Propensión , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
18.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33540684

RESUMEN

N6-methyladenosine (m6A) modification on RNA plays an important role in tumorigenesis and metastasis, which could change gene expression and even function at multiple levels such as RNA splicing, stability, translocation, and translation. In this study, we aim to conduct a comprehensive analysis on m6A RNA methylation-related genes, including m6A RNA methylation regulators and m6A RNA methylation-modified genes, in liver hepatocellular carcinoma, and their relationship with survival and clinical features. Data, which consist of the expression of widely reported m6A RNA methylation-related genes in liver hepatocellular carcinoma from The Cancer Genome Atlas (TCGA), were analyzed by one-way ANOVA, Univariate Cox regression, a protein-protein interaction network, gene enrichment analysis, feature screening, a risk prognostic model, correlation analysis, and consensus clustering analysis. In total, 405 of the m6A RNA methylation-related genes were found based on one-way ANOVA. Among them, DNA topoisomerase 2-alpha (TOP2A), exodeoxyribonuclease 1 (EXO1), ser-ine/threonine-protein kinase Nek2 (NEK2), baculoviral IAP repeat-containing protein 5 (BIRC5), hyaluronan mediated motility receptor (HMMR), structural maintenance of chromosomes protein 4 (SMC4), bloom syndrome protein (BLM), ca-sein kinase I isoform epsilon (CSNK1E), cytoskeleton-associated protein 5 (CKAP5), and inner centromere protein (INCENP), which were m6A RNA methylation-modified genes, were recognized as the hub genes based on the protein-protein interaction analysis. The risk prognostic model showed that gender, AJCC stage, grade, T, and N were significantly different between the subgroup with the high and low risk groups. The AUC, the evaluation parameter of the prediction model which was built by RandomForest, was 0.7. Furthermore, two subgroups were divided by consensus clustering analysis, in which stage, grade, and T differed. We identified the important genes expressed significantly among two clusters, including uridine-cytidine kinase 2 (UCK2), filensin (BFSP1), tubulin-specific chaperone D (TBCD), histone-lysine N-methyltransferase PRDM16 (PRDM16), phosphorylase b ki-nase regulatory subunit alpha (PHKA2), serine/threonine-protein kinase BRSK2 (BRSK2), Arf-GAP with coiled-coil (ACAP3), general transcription factor 3C polypep-tide 2 (GTF3C2), and guanine nucleotide exchange factor MSS4 (RABIF). In our study, the m6A RNA methylation-related genes in liver hepatocellular carcinoma were analyzed systematically, including the expression, interaction, function, and prognostic values, which provided an important theoretical basis for m6A RNA methylation in liver cancer. The nine important m6A-related genes could be prognostic markers in the survival time of patients.


Asunto(s)
Adenosina/análogos & derivados , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Mapas de Interacción de Proteínas , ARN/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Metilación , Modelos Biológicos , Proteínas de Neoplasias/análisis , Pronóstico , ARN/química , Análisis de Secuencia de ARN
19.
Cell Prolif ; 54(4): e13015, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33630390

RESUMEN

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a common malignant tumour with high morbidity and mortality. Metabolic regulation by oncogenes is necessary for tumour growth. Testes-specific protease 50 (TSP50) has been found to promote cell proliferation in multiple tumour types. However, the mechanism that TSP50 promotes HCC progression are not known. METHODS: Hepatocyte proliferation was analysed by MTT and BrdU incorporation after TSP50 transfection. Furthermore, LC-MS/MS, co-immunoprecipitation and GST pull-down assays were performed to analyse protein(s) binding to TSP50. Moreover, the site-specific mutation of G6PD was used to reveal the key site critical for G6PD acetylation mediated by TSP50. Finally, the role of G6PD K171 acetylation regulated by TSP50 in cell proliferation and tumour formation was investigated. RESULTS: Our data suggest that the overexpression of TSP50 accelerates hepatocyte proliferation. In addition, G6PD is an important protein that binds to TSP50 in the cytoplasm. TSP50 activates G6PD activity by inhibiting the acetylation of G6PD at the K171 site. In addition, TSP50 promotes the binding of G6PD to SIRT2. Furthermore, the K171ac of G6PD regulated by TSP50 is required for TSP50-induced cell proliferation in vitro and tumour formation in vivo. Additionally, according to The Cancer Genome Atlas (TCGA) programme, TSP50 and G6PD are negatively correlated with the survival of HCC patients. CONCLUSIONS: Collectively, our findings demonstrate that TSP50-induced cell proliferation and tumour formation are mediated by G6PD K171 acetylation.


Asunto(s)
Carcinoma Hepatocelular/patología , Glucosafosfato Deshidrogenasa/metabolismo , Neoplasias Hepáticas/patología , Serina Endopeptidasas/metabolismo , Acetilación , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Línea Celular , Proliferación Celular , Femenino , Glucosafosfato Deshidrogenasa/genética , Hepatocitos/citología , Hepatocitos/metabolismo , Humanos , Metabolismo de los Lípidos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Ratones , Ratones Desnudos , Mutagénesis Sitio-Dirigida , Unión Proteica , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Serina Endopeptidasas/química , Serina Endopeptidasas/genética , Tasa de Supervivencia , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Medicine (Baltimore) ; 100(3): e24153, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33546030

RESUMEN

BACKGROUND: Previous studies have reported that lymphocyte-to-monocyte ratio (LMR) had novel prognostic value in hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to synthetically evaluate the prognostic role of preoperative LMR in HCC patients following curative resection. METHODS: Eligible studies were acquired through searching Pubmed, Web of Science, Cochrane Library and EMbase update to September 2019. Merged hazard ratios (HRs) and 95% confidence intervals (CIs) were applied as effect sizes. RESULTS: A total of ten studies containing 4,092 patients following liver resection were enrolled in this meta-analysis. The pooled results demonstrated that preoperative elevated LMR indicated superior survival outcome (HR: 0.58, 95% CI: 0.34-0.96, P = .035) and recurrence-free survival (RFS)/disease-free survival/time to recurrence (HR = 0.76, 95% CI: 0.58-0.98, P = .034). The significant prognostic role of preoperative LMR was detected in the subgroup of all publication year, country of origin, sample sizes <300, TNM stage of I-IV and LMR cut-off value ≤4. Furthermore, high LMR was significantly associated with male, high AFP, large tumor size, incomplete tumor capsule, advanced TNM stage and BCLC stage, and presence of PVTT. CONCLUSION: Elevated preoperative LMR indicated superior survival outcome in HCC patients following curative resection, and might serve as a novel prognostic biomarker.


Asunto(s)
Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Hepatectomía , Humanos , Hígado/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Recuento de Linfocitos
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