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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.
Ann Ital Chir ; 92: 361-364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34524110

RESUMO

Spontaneous liver hemorrhage (SLH) is a serious, extremely rare, and life-threatening occurrence requiring a multidisciplinary approach. Since diagnosis might be difficult, a high mortality rate is reported. Survival depends on a prompt diagnosis followed by an appropriate management. If left untreated, SLH progresses, in fact, to a hemorrhagic shock and death. SLH is rarely idiopathic, whereas more commonly is secondary to severe preeclampsia and HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome, hepatocellular carcinoma (HCC), adenoma, focal nodular hyperplasia or hemangioma, and connective tissue diseases. We report two patients presenting with an idiopathic SLH successfully treated with angioembolization, and the results of an extensive literature review. KEY WORDS: Intrahepatic hematoma, Spontaneous liver hemorrhage, Spontaneous liver rupture.


Assuntos
Carcinoma Hepatocelular , Síndrome HELLP , Hepatopatias , Neoplasias Hepáticas , Feminino , Síndrome HELLP/diagnóstico , Síndrome HELLP/terapia , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Fígado , Hepatopatias/diagnóstico , Hepatopatias/terapia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Gravidez , Ruptura Espontânea
5.
World J Surg Oncol ; 19(1): 228, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348726

RESUMO

PURPOSES: The purposes of this study were to assess the correlation between the plasma level of Hsp90α and the clinicopathological characteristics of patients with liver cancer and compare the diagnostic efficacy of Hsp90α, AFP, CEA, and CA199 in HCC. EXPERIMENTAL DESIGN: A total of 200 individuals, including 140 patients with liver cancer or benign liver diseases and 60 healthy people, were enrolled for quantitative measurement of plasma Hsp90α by ELISA. RESULTS: The plasma level of Hsp90α was significantly different between patients with liver cancer or benign liver diseases and healthy controls (P < 0.001). The sensitivity, specificity, and AUC (95% CI) of Hsp90α were 93.2%, 85.4%, and 0.931% (0.891-0.972%), respectively, when Hsp90α was applied to differentiate liver cancer patients and healthy controls. Significant positive correlations between the plasma Hsp90α level and clinicopathological characteristics such as the history of basic liver disease (P = 0.038), active stage of hepatitis (P = 0.039), Child-Pugh score (P < 0.001), size of focal liver lesions (P = 0.004), and extrahepatic metastasis (P < 0.001) were observed. AFP + Hsp90α was the best combination strategy for the auxiliary diagnosis of HCC, with a sensitivity of 95.7%, a specificity of 97.5%, and an AUC of 0.990 (0.976-1.000). The level of plasma Hsp90α decreased significantly (P < 0.001) after resection of tumor tissue. CONCLUSIONS: This study demonstrated that plasma Hsp90α levels are useful as a diagnostic biomarker in liver cancer and may predict the responses of patients with liver cancer to surgery. Some clinicopathological characteristics could affect the plasma Hsp90α levels.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Proteínas de Choque Térmico HSP90 , Humanos , Neoplasias Hepáticas/diagnóstico , Prognóstico
6.
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
7.
Zhonghua Yi Xue Za Zhi ; 101(32): 2544-2551, 2021 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-34407581

RESUMO

Objective: To evaluate the cost-effectiveness of anti-tumor associated antigen autoantibody (TAAb) for hepatocellular carcinoma (HCC) screening in cirrhosis population with chronic hepatitis B (CHB). Methods: A simulated cohort of 40-year-old patients with CHB cirrhosis was established with a sample size of 10 000. Using TAAb screening alone or TAAb and AFP screening in parallel (TAAb + AFP) as the research strategy, and liver ultrasound and AFP screening in parallel (liver ultrasound + AFP) as the control strategy, the decision analysis Markov model was constructed and the model validity was evaluated. The 6-month cycle was simulated using TreeAge Pro 2020 software. Cost and quality-adjusted life years (QALY) were calculated. Incremental cost-effectiveness ratio (ICER) was used to compare the two strategies, and sensitivity analysis was used to evaluate the uncertainty of results. Results: The Markov model had a total of 11 outcomes, of which 7 were natural outcomes and 4 wereclinical intervention outcomes, and the goodness of fit was 0.969. The lifetime screening cost of TAAb+AFP strategy for HCC screening was 249 612 yuan/case, and the QALY per capita was 7.704 years. Compared with liver ultrasound +AFP strategy (247 805 yuan/case), the total health cost increased by 1 807 yuan/case, and the QALY obtained was 0.014. The ICER was 127 635 yuan /QALY. When the TAAb screening fee was higher than 889.552 yuan, or the discount rate was higher than 0.068, or the antiviral treatment compliance was lower than 45.1%, ICER > 212 676 yuan /QALY. When the single TAAb screening fee was 400-600 yuan, the TAAB+AFP strategy had cost effective value. When the willingness to pay was 70 892, 141 784 and 212 676 yuan /QALY, the probability of cost-effectiveness of TAAb+AFP strategy was 70.6%, 75.3% and 77.8%, respectively. Conclusion: It is cost-effective to use TAAb+AFP for early screening of liver cancer in Chinese population with CHB cirrhosis.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Adulto , Análise Custo-Benefício , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática , Neoplasias Hepáticas/diagnóstico
8.
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
9.
Medicina (Kaunas) ; 57(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34441056

RESUMO

Hepatocellular carcinoma (HCC) typically presents in patients with a chronic liver disease and rarely develops in healthy liver, especially within an accessory liver lobe. We present a case of a healthy 64-years-old woman who showed a serum alpha-fetoprotein (AFP) value of 226.3 µg/mL during a screening blood test. Past medical history was negative for chronic liver disease or cirrhosis. Intraoperative finding was an ovaloid mass connected with the second hepatic segment by a thin pedicle of hepatic tissue. Lesion was safely resected by laparoscopic approach. Histopathology analysis showed a trabecular hepatocellular carcinoma. After a 6-month follow up, there was no evidence of recurrent disease. This case report showed how serum AFP remains a highly sensitive marker, although the presentation of HCC was unusual. To our knowledge, this is the second case reported in the literature.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/diagnóstico , Pessoa de Meia-Idade , alfa-Fetoproteínas
10.
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
11.
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
12.
Medicine (Baltimore) ; 100(33): e26982, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414976

RESUMO

OBJECTIVE: : To study the correlation between alcohol consumption and the risks of liver, esophageal squamous cell carcinoma (ESCC), and gastric cancers in China mainland by meta-analysis. METHODS: : We systematically searched electronic databases to identify the case-control studies that reported the association between alcohol consumption and the risks of liver, ESCC, and gastric cancers from January 1, 2010 to April 1, 2020. The Newcastle-Ottawa Scale (NOS) was used to evaluate literature quality, and I2 analyzes were used to evaluate the heterogeneity. RESULTS: : A total of 2855-related studies were retrieved. After conditional screening, we included 26 case-control studies for meta-analysis. Meta-analysis showed that alcohol consumption was associated with increased risks of liver, ESCC, and gastric cancers (total pooled odds ratio [OR], 1.83; 95% confidence interval [CI], 1.58-2.11; liver cancer OR, 1.83; 95% CI, 1.39-2.40; ESCC OR, 2.00; 95% CI, 1.66-2.40; gastric-cancer OR, 1.54; 95% CI, 1.10-2.15). Subgroup analysis results showed that the pooled ORs of volume of alcohol consumed, years of drinking, age of starting drinking, and drinking status were 1.71 (95% CI, 1.36-2.15), 1.65 (95% CI, 1.33-2.06), 1.38 (95% CI, 0.98-1.94), and 2.00 (95% CI, 1.42-2.81), respectively. Regression analysis showed that geographical region was a source of heterogeneity. CONCLUSION: : Alcohol consumption increased the risks of liver cancer, ESCC, and gastric cancers in China. Volume of alcohol consumed, years of drinking, age of starting drinking, and drinking status were all significant factors for these risks.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Esofágicas/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , China/epidemiologia , Correlação de Dados , Neoplasias Esofágicas/epidemiologia , Humanos , Neoplasias Hepáticas/epidemiologia , Razão de Chances , Neoplasias Gástricas/epidemiologia
13.
In Vivo ; 35(5): 2963-2968, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410995

RESUMO

BACKGROUND: The liver is the digestive organ where metastatic adenocarcinoma of unknown primary site is most often observed. CASE REPORT: A 74-year-old man was diagnosed with a growing gallbladder tumor and multiple liver tumors limited to the left lateral sector. Liver tumors were suggested to be primary or secondary adenocarcinoma with no relation to the gallbladder tumor. Also for diagnostic purposes, laparoscopic full-thickness resection of the gallbladder, laparoscopic lateral sectionectomy and lymph node sampling were performed. The final histopathological diagnosis was hyperplastic polyp of the gallbladder and metastatic poorly differentiated adenocarcinoma of the liver. Liver tumors were suspected to originate from the stomach, duodenum, or small intestine; however, the primary sites could not be identified. The patient has been closely followed up without any chemotherapy 3 months after surgery. CONCLUSION: Laparoscopic surgery can be strongly recommended for patients with multiple liver tumors of unknown origin concomitant with a gallbladder tumor.


Assuntos
Adenocarcinoma , Neoplasias da Vesícula Biliar , Laparoscopia , Neoplasias Hepáticas , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Idoso , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Masculino
14.
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
15.
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
16.
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
17.
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
18.
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
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 263: 120181, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34311164

RESUMO

Liver cancer is the most common fatal malignant tumor in the world. Early diagnosis of liver cancer can improve the survival rate of the patients with liver disease. In this paper, Fourier transform infrared (FTIR) spectroscopy combined with curve fitting and chemometrics was used to distinguish the serum from patients from that of healthy people. The curve fitting results in protein range of 1700-1600 cm-1 showed that there were differences in the secondary structure of protein in serum between the patients with liver cancer and healthy people. Principal component analysis (PCA) in lipid range of 2900-2800 cm-1 could distinguish the serum of patients with liver cancer from that of healthy people. The first two principal components PC1 and PC2 explained 95% of the total data variance. The sensitivity and specificity of partial least squares discriminant analysis (PLS-DA) in lipid range of 2900-2800 cm-1 reached 92.85% and 95.23% respectively. It is shown that FTIR spectroscopy might be developed as an effective method for the diagnosis of liver cancer.


Assuntos
Neoplasias Hepáticas , Análise Discriminante , Análise de Fourier , Humanos , Análise dos Mínimos Quadrados , Neoplasias Hepáticas/diagnóstico , Análise de Componente Principal , Espectroscopia de Infravermelho com Transformada de Fourier
20.
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
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