Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.543
Filtrar
1.
Gene ; 806: 145935, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478821

RESUMO

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 186), liver cirrhosis (LC, n = 142) and hepatocellular carcinoma (HCC, n = 223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR = 1.6; 95%CI = 1.1-2.3; p = 0.0087) and disease progression (LC vs. CHB: OR = 1.8; 95%CI = 1.1-2.9; p = 0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p < 0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C > B > A, p < 0.0001) and BCLC classification (BCLC D > C > B > A, p = 0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.


Assuntos
Antígeno B7-H1/genética , Carcinoma Hepatocelular/genética , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Regiões 3' não Traduzidas , Adulto , Idoso , Antígeno B7-H1/sangue , Biomarcadores/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Expressão Gênica , Predisposição Genética para Doença , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
2.
Zhonghua Gan Zang Bing Za Zhi ; 29(8): 781-787, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34517461

RESUMO

Objective: To explore the value of Krüppel-like factor 5 (KLF5), a family member of the zinc finger protein transcription factor, in the diagnosis and prognostic evaluation of hepatocellular carcinoma (HCC). Methods: Cancerous and non-cancerous tissues were collected from 126 cases after HCC surgery by self-matching method with microarray fabrication. Immunohistochemistry was used to analyze the expression of KLF5, clinicopathological characteristics and prognostic value. The sera of 222 cases with chronic liver disease were collected and their KLF5 levels were quantitatively determined by enzyme-linked immunosorbent assay (ELISA). Simultaneously, 40 normal human sera were used as controls to evaluate the value of abnormal KLF5 in the diagnosis and differentiation of benign and malignant liver diseases. T-test, Z-test and χ (2) test were performed on the data. Results: The positive expression rate of KLF5 in the HCC group was 95.2% (120/126), which was significantly higher than the non-cancerous group 38.9% (49/126; χ (2) = 14.385, P < 0.001). KLF5 expression was significantly correlated with TNM stage (stage I 35%, stage II 40%, stage III 74.4%, stage IV 78.1%), tumor size, alpha fetoprotein (AFP) concentration, portal vein embolism, HBV infection and 5-year survival rate. Univariate/multivariate analysis showed that KLF5 high expression was an independent predictor of HCC prognosis. The serum KLF5 level was significantly higher in HCC patients than liver cirrhosis, chronic hepatitis and normal control group (P < 0.001). With the serum KLF5 > 800 ng/ml and AFP > 25 µg/L as limit, the positive rates for HCC diagnosis were 90.48% and 73.81%, respectively, which were lower than the AFP specificity and false positive rate, and was helpful for the differential diagnosis of benign and malignant liver diseases. Conclusion: The overexpression of KLF5 in liver cancer tissues and blood is closely related to the HCC clinical stage and prognosis. Moreover, KLF5 analysis is helpful for HCC diagnosis and differential diagnosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Humanos , Fatores de Transcrição Kruppel-Like , Neoplasias Hepáticas/diagnóstico , Prognóstico , Fatores de Transcrição , Zinco , Dedos de Zinco , alfa-Fetoproteínas
3.
Zhonghua Gan Zang Bing Za Zhi ; 29(8): 788-793, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34517462

RESUMO

Objective: To study the changes of urinary metabolic profile, screen metabolic ions characterization with clinical diagnostic value, and a disease differentiation model establishment, in an attempt to help the clinical diagnosis of hepatocellular carcinoma patients. Methods: A case-control study was conducted. Ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) were used to analyze urine samples of 32 patients with hepatocellular carcinoma, 28 patients with liver cirrhosis and 28 healthy persons, respectively. The orthogonal partial least squares discriminant analysis (OPLS-DA) and the principal component analysis (PCA) model were constructed using MZmine2.0 and SIMCA-P + 12.0.1.0 software for preliminary screening of metabolites. The metabolic ions selected in the final test were analyzed by SPSS, and the markers were analyzed and screened by one-way analysis of variance. Finally, the sensitivity and specificity of the selected markers were analyzed by calculating the area under the receiver operating characteristic (ROC) curve. One-way analysis of variance was used to compare quantitative indicators between groups. Results: OPLS-DA model parameters were R2X = 35.3%, R2Y = 86.9%, and Q2 = 72.2%, which had a good identification value. A total of 26 characteristic ions were screened, of which 17 were identified. 14, 19-Dihydroaspidospermatine had a high value in distinguishing healthy person with hepatocellular carcinoma patients, and the area under the receiver operating characteristic curve was higher than 0.9. The area under the ROC curve for distinguishing liver cancer with liver cirrhosis patients was 0.88, which was higher than the ROC curve of alpha-fetoprotein (0.75). Conclusion: Based on the UPLC-MS platform, the PCA and OPLS-DA models were successfully constructed, and the characteristic metabolic ions in the urine were extracted and identified, which has a certain value in assisting clinical screening of hepatocellular carcinoma patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Estudos de Casos e Controles , Cromatografia Líquida , Humanos , Metaboloma , Metabolômica , Espectrometria de Massas em Tandem
4.
World J Gastroenterol ; 27(28): 4687-4696, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34366629

RESUMO

BACKGROUND: Diagnostic accuracy of various tumor markers and their combinations for hepatocellular carcinoma (HCC) was not fully investigated. AIM: To evaluate the diagnostic accuracy of alpha-fetoprotein (AFP), the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) and their combination for HCC diagnosis. METHODS: Patients with newly detected liver mass or elevated serum AFP levels were considered eligible. Serum AFP level, AFP-L3 fraction, and PIVKA-II level were measured at the first visit. RESULTS: In total, 622 patients were included; 355 patients (57.1%) had chronic liver disease, and 208 (33.4%) had liver cirrhosis. HCC was diagnosed in 160 patients (25.7%). The area under the receiver operating characteristics curves (AUROCs) of the serum AFP, AFP-L3 fraction, AFP-L3, and PIVKA-II levels for the diagnosis of HCC were 0.775, 0.792, 0.814, and 0.834, respectively. A novel diagnostic model was developed by classifying patients in a 1:1 ratio into training and validation sets. Using the binary regression analysis of the training cohort, the AFP, AFP-L3 fraction, and PIVKA-II (ALPs) score was calculated as follows: ALPs score = 3.8 × [serum AFP level (ng/mL) × AFP-L3 fraction (%) × 0.01] + 0.2 × PIVKA-II level (mAU/mL). The AUROC of the ALPs score for diagnosis of HCC was 0.878, significantly higher than that of serum AFP level (P < 0.001), AFP-L3 fraction (P < 0.001), PIVKA-II level (P = 0.036), and AFP-L3 level (P = 0.006). The optimal ALPs score cut-off was 5.3 (sensitivity, 85.0%, specificity 80.1%). The validation cohort showed similar results. CONCLUSION: The ALPs score calculated using serum AFP level, AFP-L3 fraction, and PIVKA-II level showed improved accuracy in HCC diagnosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Lectinas de Plantas , Precursores de Proteínas , Protrombina , alfa-Fetoproteínas
5.
Medicine (Baltimore) ; 100(33): e26948, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414957

RESUMO

ABSTRACT: Aberrant immunity has been associated with the initiation and progression of cancers such as hepatocellular carcinoma (HCC). Here, we aim to develop a signature based on immune-related genes (IRGs) to predict the prognosis of HCC patients. The gene expression profiles of 891 HCC samples were derived from 4 publicly accessible datasets. A total of 1534 IRGs from Immunology Database and Analysis Portal website were obtained as candidate genes for prognostic assessment. Using least absolute shrinkage and selection operator (LASSO) regression analysis, 12 IRGs were selected as prognostic biomarkers and were then aggregated to generate an IRG score for each HCC sample. In the training dataset (n = 365), patients with high IRG scores showed a remarkably poorer overall survival than those with low IRG scores (log-rank P < .001). Similar results were documented in 3 independent testing datasets (n = 226, 221, 79, respectively). Multivariate Cox regression and stratified analyses indicated that the IRG score was an independent and robust signature to predict the overall survival in HCC patients. Patients with high IRG scores tended to be in advanced TNM stages, with increased risks of tumor recurrence and metastasis. More importantly, the IRG score was strongly associated with certain immune cell counts, gene expression of immune checkpoints, estimated immune score, and mutation of critical genes in HCC. In conclusion, the proposed IRG score can predict the prognosis and reflect the tumor immune microenvironment of HCC patients, which may facilitate the individualized treatment and provide potential immunotherapeutic targets.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Imunidade/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Transcriptoma , Microambiente Tumoral/imunologia
6.
BMC Health Serv Res ; 21(1): 846, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419018

RESUMO

BACKGROUND: The PAGE-B score (Platelet Age GEnder-HBV) selects chronic hepatitis B (cHB) patients showing no relevant 5-year risk for hepatocellular carcinoma (HCC). We, therefore, explored potential cost reduction following the introduction of a PAGE-B tailored ultrasound screening in a single center cohort of cHB patients receiving stable antiviral therapy. METHODS: cHB patients attending throughout the year 2018 were documented. Patients eligible for PAGE-B score were classified into high (≥18 points), intermediate (10-17 points) and low (≤9 points) HCC risk groups. Patients of the low HCC risk group could postpone HCC screening to reduce HCC screening expenses. Full costs for hepatic ultrasound were assessed. RESULTS: Throughout the year cHB patients (n = 607) attended our clinic, which included PAGE-B eligible patients (n = 227, 37.4%) of whom n = 94 (15.8%) were allocated to the low HCC risk group. Sonographic HCC screening during a median exam time of 12.4 min (IQR 9.2-17.2) resulted in total costs of 22.82 Euro/exam. Additional opportunistic expenses caused by patient's lost earnings or productivity were 15.6-17.5 €/exam and 26.7 €/exam, respectively. Following a PAGE-B tailored HCC screening at our institution annual full costs for cHB patients could be reduced by 15.51%, which equals a cost reduction by 1.91% for our total sonography unit. In comparison, 1.35% up to 7.65% of HBV-infected patients of Caucasian descent could postpone HCC screening according to population-based estimates from Germany. CONCLUSIONS: PAGE-B risk score adapted screening for HCC is an efficient and cost neutral tool to reduce costs for sonography in Caucasian patients with chronic hepatitis B receiving antiviral treatment.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Fatores de Risco , Ultrassonografia
7.
PLoS One ; 16(8): e0256544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34437610

RESUMO

BACKGROUND: Patients with hepatocellular carcinoma (HCC) represent a vulnerable population potentially negatively affected by COVID-19-associated reallocation of healthcare resources. Here, we report the impact of COVID-19 on the management of HCC patients in a large tertiary care hospital. METHODS: We retrospectively analyzed clinical data of HCC patients who presented at the Vienna General Hospital, between 01/DEC/2019 and 30/JUN/2020. We compared patient care before (period 1) and after (period 2) implementation of COVID-19-associated healthcare restrictions on 16/MAR/2020. RESULTS: Of 126 patients, majority was male (n = 104, 83%) with a mean age of 66±11 years. Half of patients (n = 57, 45%) had impaired liver function (Child-Pugh stage B/C) and 91 (72%) had intermediate-advanced stage HCC (BCLC B-D). New treatment, was initiated in 68 (54%) patients. Number of new HCC diagnoses did not differ between the two periods (n = 14 vs. 14). While personal visits were reduced, an increase in teleconsultation was observed (period 2). Number of patients with visit delays (n = 31 (30%) vs. n = 10 (10%); p = 0.001) and imaging delays (n = 25 (25%) vs. n = 7 (7%); p = 0.001) was higher in period 2. Accordingly, a reduced number of patients was discussed in interdisciplinary tumor boards (lowest number in April (n = 24), compared to a median number of 57 patients during period 1). Median number of elective/non-elective admissions was not different between the periods. One patient contracted COVID-19 with lethal outcome. CONCLUSIONS: Changes in patient care included reduced personal contacts but increased telephone visits, and delays in diagnostic procedures. The effects on long-term outcome need to be determined.


Assuntos
COVID-19/epidemiologia , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , COVID-19/virologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Diagnóstico Tardio , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pandemias , Pacientes/psicologia , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Taxa de Sobrevida , Telemedicina , Centros de Atenção Terciária
8.
J Transl Med ; 19(1): 359, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412629

RESUMO

BACKGROUND: Although an association between the cytochrome P4502D6 (CYP2D6) *10 (100C>T) polymorphism and hepatocellular carcinoma (HCC) is known, the mechanism remains unclear. Here we aimed to explore mechanisms of CYP2D6*10 (100C>T) polymorphism conferring to HCC, and screen markers for HCC. METHODS: Label-free global proteome profiling with 34 normal livers and peritumor tissue from 61 HCC patients was performed, and angiopoietin-like protein-6 (ANGPTL6) was evaluated in 2 liver samples validation cohorts and 2 blood specimens validation cohorts. RESULTS: We found a significantly decreased frequency of TT in HCC patients which reduced HCC susceptibility by 69.2% and was accompanied by lowered enzymatic activity for CYP2D6. Proteomic analysis revealed 1342 differentially expressed proteins (DEPs) that were associated with HCC and 88 DEPs were identified as 100 TT-related proteins, likely underlying the susceptibility to HCC. Twenty-two upregulated DEPs and 66 downregulated DEPs were mainly related to lipid metabolism and the extracellular matrix, respectively. High ANGPTL6 was associated with a higher risk to HCC and worse prognosis. ANGPTL6 was both an independent risk factor and an independent prognostic factor for HCC and exhibited strong potential for predicting HCC occurrence, with comparable AUC values and higher sensitivity compared with alpha-fetoprotein. CONCLUSIONS: The TT genotype-associated decreased risk of HCC appears to be related to lowered CYP2D6 activity and altered protein expression in the tumor microenvironment, and ANGPTL6 is a promising new diagnostic and prognostic biomarker for HCC. Our findings reveal new mechanistic insights for polymorphisms related to HCC risk and provide avenues for screening for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas Semelhantes a Angiopoietina/genética , Biomarcadores , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Citocromo P-450 CYP2D6/genética , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Prognóstico , Proteômica , Microambiente Tumoral
9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(4): 710-715, 2021 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-34393233

RESUMO

OBJECTIVE: LAPTM4B-35 protein is one of the isoforms that are encoded by a cancer driver gene, LAPTM4B. This gene was primarily found and identified in our lab of Peking University School of Basic Medical Sciences. The LAPTM4B-35 protein and its encoded mRNA are significantly over-expressed in a variety of cancers, such as hepatocellular carcinoma (HCC), lung cancers (including non small-cell lung cancer and small-cell lung cancer), stomach cancer, colorectal carcinoma, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, and so on. It has firmly demonstrated through lab experiments either in vivo or in vitro, as well as clinical studies that the over-expression of LAPTM4B-35 can promote cancer growth, metastasis, and multidrug resistance. Specially, the expressive level of LAPTM4B-35 is associa-ted with recurrence of HCC. The aim of this study is to identify the release of LAPTM4B-35 protein from hepatocellular carcinoma into blood of HCC patients and into the medium of cultured HCC cells, and to identify its possible form of LAPTM4B-35 protein existed in blood and cell culture medium, as well as to explore the possibility of LAPTM4B-35 protein as a novel HCC biomarker for diagnosis of HCC and prognosis of HCC patients. METHODS: Immunobloting (Western blot) and enzyme-linked immunosorbent assay (ELISA) were used for identification of LAPTM4B-35 protein in the blood of HCC patients and normal individuals. Ultrafiltration and ultracentrifugation were used to isolate and purify exosomes from the culture medium of HCC cells. RESULTS: LAPTM4B-35 protein existed in the blood from HCC patients and normal donors that were demonstrated through Western blot and ELISA. LAPTM4B-35 was also released into the culture medium of HCC cells in the form of exosomes. Preliminary experiments showed that the average and the median of LAPTM4B-35 protein level in the blood of HCC patients (n=43) were both significantly higher than that in the blood of normal donors (n=33) through sandwich ELISA. CONCLUSION: It is promising that the LAPTM4B-35 protein which is released from HCC cells in the form of exosomes into their extraenvironment may be exploited as a novel cancer biomarker for HCC serological diagnosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Proteínas de Membrana/genética , Proteínas Oncogênicas , Prognóstico
10.
Bioengineered ; 12(1): 4054-4069, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34369278

RESUMO

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Carcinoma Hepatocelular/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Receptores Virais/genética , alfa-Fetoproteínas/genética , Fatores Etários , Idoso , Enzima de Conversão de Angiotensina 2/metabolismo , Área Sob a Curva , COVID-19/virologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/classificação , Proteínas de Neoplasias/metabolismo , Fatores de Proteção , Mapeamento de Interação de Proteínas , Curva ROC , Receptores Virais/metabolismo , SARS-CoV-2/patogenicidade , Análise de Sobrevida , alfa-Fetoproteínas/metabolismo
11.
Medicine (Baltimore) ; 100(30): e26762, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397721

RESUMO

ABSTRACT: Reliable biomarkers are of great significance for the treatment and diagnosis of hepatocellular carcinoma (HCC). This study identified potential prognostic epithelial-mesenchymal transition related lncRNAs (ERLs) by the cancer genome atlas (TCGA) database and bioinformatics.The differential expression of long noncoding RNA (lncRNA) was obtained by analyzing the lncRNA data of 370 HCC samples in TCGA. Then, Pearson correlation analysis was carried out with EMT related genes (ERGs) from molecular signatures database. Combined with the univariate Cox expression analysis of the total survival rate of hepatocellular carcinoma (HCC) patients, the prognostic ERLs were obtained. Then use "step" function to select the optimal combination of constructing multivariate Cox expression model. The expression levels of ERLs in HCC samples were verified by real-time quantitative polymerase chain reaction.Finally, we identified 5 prognostic ERLs (AC023157.3, AC099850.3, AL031985.3, AL365203.2, CYTOR). The model showed that these prognostic markers were reliable independent predictors of risk factors (P value <.0001, hazard ratio [HR] = 2.400, 95% confidence interval [CI] = 1.667-3.454 for OS). In the time-dependent receiver operating characteristic analysis, this prognostic marker is a good predictor of HCC survival (area under the curve of 1 year, 2 years, 3 years, and 5 years are 0.754, 0.720, 0.704, and 0.662 respectively). We analyzed the correlation of clinical characteristics of these prognostic markers, and the results show that this prognostic marker is an independent factor that can predict the prognosis of HCC more accurately. In addition, by matching with the Molecular Signatures Database, we obtained 18 ERLs, and then constructed the HCC prognosis model and clinical feature correlation analysis using 5 prognostic ERLs. The results show that these prognostic markers have reliable independent predictive value. Bioinformatics analysis showed that these prognostic markers were involved in the regulation of EMT and related functions of tumor occurrence and migration.Five prognostic types of ERLs identified in this study can be used as potential biomarkers to predict the prognosis of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Prognóstico
12.
Biosens Bioelectron ; 192: 113500, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34280653

RESUMO

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. Circ-CDYL, one of the circular RNAs (circRNAs), is recognized as an independent marker for HCC early diagnosis. Point-of-care testing (POCT) of circRNA is essential and in great demand for clinical applications. Herein, we report a fully integrated electrochemical POCT platform for circRNA detection based on Au nanoflowers (AuNFs)/peptide nucleic acid (PNA) modified carbon-fiber microelectrode (CFME). PNA is applied as the recognition element, highly specified for a back-splice junction of circRNA. AuNFs increased active site for PNA probes, improving target-capturing efficiency at an ultralow level. The platform provides a linear range of 10 fM to 1 µM, with a detection limit as low as 3.29 fM. This biosensor demonstrates high specificity towards one-base mismatch and is stable for up to 24 days. The analytical performance has also been verified in human serum samples, demonstrating the potential utility in clinical POCT applications for HCC.


Assuntos
Técnicas Biossensoriais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Testes Imediatos , RNA Circular
13.
Zhonghua Gan Zang Bing Za Zhi ; 29(6): 515-522, 2021 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-34192841

RESUMO

Primary hepatocellular carcinoma is one of the most common malignancies worldwide. Half of the annual newly diagnosed liver cancer cases come from China. A large number of clinical studies and practices have proved that early screening and early diagnosis can effectively reduce the 5-year total mortality of liver cancer. Therefore, it is extremely urgent to explore and establish customized liver cancer screening strategies for China. Based on the relevant domestic and foreign guidelines, clinical practice, and the latest advances in the research of the PreCar project, the expert from PreCar project(Prospective suRveillance for very Early hepatoCellular cARcinoma, PreCar), proposed novel strategies and procedures for early liver cancer screening in my country. The PreCar project aims to provide practical methods for early liver cancer screening and diagnosis, and to improve our national prophylactic level for liver cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , China/epidemiologia , Consenso , Detecção Precoce de Câncer , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Estudos Prospectivos
14.
Medicine (Baltimore) ; 100(27): e26489, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232180

RESUMO

ABSTRACT: To analyze the correlation between quantitative contrast-enhanced ultrasonography (CEUS) parameters and angiogenesis in primary small hepatocellular carcinoma (sHCC) with varying degrees of differentiation.According to varying degrees of differentiation, a total of 90 primary sHCC patients admitted to our hospital from July 2018 to January 2020 were selected and divided into poorly differentiated group (24 cases), moderately differentiated group (31 cases), and highly differentiated group (35 cases). All patients received real-time CEUS before surgery. The tumor diameter, microvascular morphology, grading of color blood flow, contrast-enhanced performance in different phases, quantitative CEUS parameters, expression of angiogenesis-related genes, and microvessel density (MVD) were compared among the 3 groups. The correlation between quantitative parameters of CEUS and angiogenesis indexes was analyzed by Spearman rank correlation analysis.Spearman rank correlation analysis showed that vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor receptor (EGFR), and angiopoietin-2 (Ang-2) expression and MVD were negatively correlated with the time to peak (TTP), wash-out time, and peak accelerating time (PAT) (r < 0, P < .05), and were positively correlated with enhancing slope rate (ESR) and peak intensity increasing rate (PIIR) (r > 0, P < .05).CEUS is able to identify varying degrees of differentiation in primary sHCC, and the quantitative CEUS parameters are closely related to angiogenesis.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Meios de Contraste/farmacologia , Neoplasias Hepáticas/diagnóstico , Microvasos/diagnóstico por imagem , Gradação de Tumores , Ultrassonografia Doppler em Cores/métodos , Adulto , Idoso , Carcinoma Hepatocelular/irrigação sanguínea , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Aging (Albany NY) ; 13(13): 17607-17628, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237706

RESUMO

The function of competitive endogenous RNA (ceRNA) network in the immune regulation of hepatocellular carcinoma (HCC) is unclear. Our study aimed to construct an immune-related ceRNA network and develop an immune-related long noncoding RNA (lncRNA) signature to assess the prognosis of HCC patients and to optimize the treatment methods. We firstly constructed a ceRNA regulatory network for HCC using differentially expressed lncRNAs, mRNAs and microRNAs (miRNAs) from the Cancer Genome Atlas. A signature was constructed by 11 immune-related prognostic lncRNAs from the ceRNA network. The survival analysis and receiver operating characteristic analysis validated the reliability of the signature. Multivariate Cox regression analysis revealed that the signature could act an independent prognostic indicator. This signature also showed high association with immune cell infiltration and immune check blockades. LINC00491 was identified as the hub lncRNA in the signature. In vitro and in vivo evidence demonstrated that silencing of LINC00491 significantly inhibited HCC growth. Finally, 59 lncRNAs, 21 miRNAs, and 26 mRNAs were obtained to build the immune-related ceRNA network for HCC. In conclusion, our novel immune-related lncRNA prognostic signature and the immune-related ceRNA network might provide in-depth insights into tumor-immune interaction of HCC and promote better individual treatment strategies in HCC patients.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , RNA Longo não Codificante/análise , RNA Longo não Codificante/genética , Animais , Carcinoma Hepatocelular/imunologia , Redes Reguladoras de Genes/genética , Inativação Gênica , Genômica , Humanos , Neoplasias Hepáticas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Aging (Albany NY) ; 13(13): 17592-17606, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237708

RESUMO

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two most common pathology subtypes of primary liver cancer (PLC). Identifying DNA methylation biomarkers for diagnosis of PLC and further distinguishing HCC from ICC plays a vital role in subsequent treatment options selection. To obtain potential diagnostic DNA methylation sites for PLC, differentially methylated CpG (DMC) sites were first screened by comparing the methylation data between normal liver samples and PLC samples (ICC samples and HCC samples). A random forest algorithm was then used to select specific DMC sites with top Gini value. To avoid overfitting, another cohort was taken as an external validation for evaluating the area under curves (AUCs) of different DMC sites combination. A similar model construction strategy was applied to distinguish HCC from ICC. In addition, we identified DNA Methylation-Driven Genes in HCC and ICC via MethylMix method and performed pathway analysis by utilizing MetaCore. Finally, we not only performed methylator phenotype based on independent prognostic sites but also analyzed the correlations between methylator phenotype and clinical factors in HCC and ICC, respectively. To diagnose PLC, we developed a model based on three PLC-specific methylation sites (cg24035245, cg21072795, and cg00261162), whose sensitivity and specificity achieved 98.8%,94.8% in training set and 97.3%,81% in validation set. Then, to further divide the PLC samples into HCC and ICC, we established another mode through three methylation sites (cg17769836, cg17591574, and cg07823562), HCC accuracy and ICC accuracy achieved 95.8%, 89.8% in the training set and 96.8%,85.4% in the validation set. In HCC, the enrichment pathways were mainly related to protein folding, oxidative stress, and glutathione metabolism. While in ICC, immune response, embryonic hepatocyte maturation were the top pathways. Both in HCC and ICC, methylator phenotype correlated well with overall survival time and clinical factors involved in tumor progression. In summary, our study provides the biomarkers based on methylation sites not only for the diagnosis of PLC but also for distinguishing HCC from ICC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/genética , Metilação de DNA/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Algoritmos , Estudos de Coortes , Diagnóstico Diferencial , Glutationa/metabolismo , Hepatócitos/patologia , Humanos , Estresse Oxidativo/genética , Valor Preditivo dos Testes , Prognóstico , Dobramento de Proteína , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Aging (Albany NY) ; 13(13): 17707-17733, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34252885

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality, which makes the prognostic prediction challenging. Angiogenesis appears to be of critical importance in the progression and metastasis of HCC. Some of the angiogenesis-related genes promote this process, while other anti-angiogenesis genes suppress tumor growth and metastasis. Therefore, the comprehensive prognostic value of multiple angiogenesis-related genes in HCC needs to be further clarified. In this study, the mRNA expression profile of HCC patients and the corresponding clinical data were acquired from multiple public databases. Univariate Cox regression analysis was utilized to screen out differentially expressed angiogenesis-related genes with prognostic value. A multigene signature was established with the least absolute shrinkage and selection operator Cox regression in the Cancer Genome Atlas cohort, and validated through an independent cohort. The results suggested that a total of 16 differentially expressed genes (DEGs) were associated with overall survival (OS) and a 7-gene signature was constructed. The risk score of each patient was calculated using this signature, the median value of which was used to divide these patients into a high-risk group and a low-risk group. Compared with the low-risk group, the patients in the high-risk group had a poor prognosis. The risk score was an independent predictor for OS through multivariate Cox regression analysis. Then, unsupervised learning was used to verify the validity of this 7-gene signature. A nomogram by further integrating clinical information and the prognostic signature was utilized to predict prognostic risk and individual OS. Functional enrichment analyses demonstrated that these DEGs were enriched in the pathways of cell proliferation and mitosis, and the immune cell infiltration was significantly different between the two risk groups. In summary, a novel angiogenesis-related genes signature could be used to predict the prognosis of HCC and for targeted therapy.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neovascularização Patológica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biologia Computacional , Bases de Dados Genéticas , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nomogramas , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Análise de Sobrevida , Adulto Jovem
18.
Yonsei Med J ; 62(8): 758-766, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34296554

RESUMO

PURPOSE: To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. MATERIALS AND METHODS: Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7-12 months (1Y), 13-24 months (2Y), and 25-36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. RESULTS: The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77; never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). CONCLUSION: HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Estudos de Coortes , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos
19.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200243

RESUMO

Hepatocellular carcinoma (HCC) exerts huge effects on the health burden of the world because of its high mortality and poor prognosis. HCC is often clinically detected late in patients. If HCC could be detected and treated earlier, the survival rate of patients will be greatly improved. Therefore, identifying specific biomarkers is urgent and important for HCC. The liver is also recognized as an immune organ. The occurrence of HCC is related to exacerbation of immune tolerance and/or immunosurveillance escape. The host immune system plays an important role in the recognition and targeting of tumor cells in cancer immunotherapy, as can be seen from the clinical success of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells. Thus, there is a pressing medical need to discover immunodiagnostic biomarkers specific to HCC for understanding the pathological mechanisms of HCC, especially for immunotherapy targets. We have reviewed the existing literature to summarize the immunodiagnostic markers of HCC, including autoantibodies against tumor-associated antigens (TAAs) and exosomes, to provide new insights into HCC and early detection of this deadly cancer.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Imunoterapia/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Animais , Carcinoma Hepatocelular/imunologia , Humanos , Neoplasias Hepáticas/imunologia , Microambiente Tumoral/imunologia
20.
BMJ Case Rep ; 14(7)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253511

RESUMO

Hepatoid adenocarcinoma (HAC) is a rare tumour that produces an alpha-fetoprotein (AFP) mimicking hepatocellular carcinoma (HCC). Adrenal HAC is exceedingly rare. Here we report extremely high AFP-producing adrenal HAC, the first case in Thailand. A 47-year-old man presented with left flank pain and weight loss for 2 months. A palpably huge left flank mass was observed on physical examination. CT revealed a 7 cm enhanced mass involving the left adrenal gland and multiple contrast-enhanced hypodense masses in both liver lobes. The largest was a 3.7 cm at liver segment-VII without cirrhotic background, with an AFP level of 321 495 ng/mL. Both adrenal and liver biopsies were performed. This patient received a diagnosis of advanced adrenal HAC. Unfortunately, the tumour progressed, causing massive upper gastrointestinal bleeding and death. Adrenal HAC is challenging to diagnose, which multifocal HCC, pheochromocytoma and adrenocortical carcinoma should be excluded. Surgical resection is preferred among resectable patients. However, no systemic therapy has been standardised.


Assuntos
Adenocarcinoma , Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Tailândia , alfa-Fetoproteínas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...