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1.
BMC Surg ; 21(1): 178, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794850

RESUMO

BACKGROUND: The inflammation indexes in blood routine play an essential role in evaluating the prognosis of patients with hepatocellular carcinoma, but the effect on early recurrence has not been clarified. The study aimed to investigate the risk factors of early recurrence (within 2 years) and recurrence-free survival after curative hepatectomy and explore the role of inflammatory indexes in predicting early recurrence. METHODS: The baseline data of 161 patients with hepatocellular carcinoma were analyzed retrospectively. The optimal cut-off value of the inflammatory index was determined according to the Youden index. Its predictive performance was compared by the area under the receiver operating characteristic curve. Logistic and Cox regression analyses were used to determine the risk factors of early recurrence and recurrence-free survival. RESULTS: The area under the curve of monocyte to lymphocyte ratio (MLR) for predicting early recurrence was 0.700, which was better than systemic inflammatory response index (SIRI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII). MLR, tumour size, tumour differentiation and BCLC stage are all risk factors for early recurrence and recurrence-free survival of HCC. Combining the above four risk factors to construct a joint index, the area under the curve for predicting early recurrence was 0.829, which was better than single MLR, tumour size, tumour differentiation and BCLC stage. Furthermore, with the increase of risk factors, the recurrence-free survival of patients is worse. CONCLUSION: The combination of MLR and clinical risk factors is helpful for clinicians to identify high-risk patients with early recurrence and carry out active postoperative adjuvant therapy to improve the prognosis of patients.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Inflamação , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Humanos , Inflamação/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Contagem de Linfócitos , Monócitos , Recidiva Local de Neoplasia/sangue , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco
2.
Medicine (Baltimore) ; 100(11): e24476, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725934

RESUMO

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.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/sangue , Hepatectomia/mortalidade , Testes de Função Hepática/métodos , Neoplasias Hepáticas/sangue , Contagem de Plaquetas , Albumina Sérica/análise , Adulto , Idoso , Biomarcadores Tumorais , Plaquetas , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Nomogramas , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
3.
BMC Surg ; 21(1): 72, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536005

RESUMO

BACKGROUND: Most hepatocellular carcinoma (HCC) patients' liver function indexes are abnormal. We aimed to investigate the relationship between (alkaline phosphatase + gamma-glutamyl transpeptidase)/lymphocyte ratio (AGLR) and the progression as well as the prognosis of HCC. METHODS: A total of 495 HCC patients undergoing radical hepatectomy were retrospectively analyzed. We randomly divided these patients into the training cohort (n = 248) and the validation cohort (n = 247). In the training cohort, receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of AGLR for predicting postoperative survival of HCC patients, and the predictive value of AGLR was evaluated by concordance index (C-index). Further analysis of clinical and biochemical data of patients and the correlation analysis between AGLR and other clinicopathological factors were finished. Univariate and multivariate analyses were performed to identify prognostic factors for HCC patients. Survival curves were analyzed using the Kaplan-Meier method. RESULTS: According to the ROC curve analysis, the optimal predictive cut-off value of AGLR was 90. The C-index of AGLR was 0.637 in the training cohort and 0.654 in the validation cohort, respectively. Based on this value, the HCC patients were divided into the low-AGLR group (AGLR ≤ 90) and the high-AGLR group (AGLR > 90). Preoperative AGLR level was positively correlated with alpha-fetoprotein (AFP), tumor size, tumor-node-metastasis (TNM) stage, and microvascular invasion (MVI) (all p < 0.05). In the training and validation cohorts, patients with AGLR > 90 had significantly shorter OS than patients with AGLR ≤ 90 (p < 0.001). Univariate and multivariate analyses of the training cohort (HR, 1.79; 95% CI 1.21-2.69; p < 0.001) and validation cohort (HR, 1.82; 95% CI 1.35-2.57; p < 0.001) had identified AGLR as an independent prognostic factor. A new prognostic scoring model was established based on the independent predictors determined in multivariate analysis. CONCLUSIONS: The elevated preoperative AGLR level indicated poor prognosis for patients with HCC; the novel prognostic scoring model had favorable predictive capability for postoperative prognosis of HCC patients, which may bring convenience for clinical management.


Assuntos
Alanina Transaminase/sangue , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Linfócitos/patologia , Adulto , Idoso , Fosfatase Alcalina/sangue , Carcinoma Hepatocelular/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , gama-Glutamiltransferase/sangue
4.
Medicine (Baltimore) ; 100(2): e24172, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466191

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the cause of an overwhelming number of cancer-related deaths across the world. Developing precise and noninvasive biomarkers is critical for diagnosing HCC. Our research was designed to explore potentially useful biomarkers of host peripheral blood mononuclear cell (PBMC) in HCC by integrating comprehensive bioinformatic analysis. METHODS: Gene expression data of PBMC in both healthy individuals and patients with HCC were extracted from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to annotate the function of DEGs. Protein-protein interaction analysis was performed to screen the hub genes from DEGs. cBioportal database analysis was performed to assess the prognostic significance of hub genes. The Cancer Cell Line Encyclopedia (CCLE) and The Human Protein Atlas (HPA) database analyses were performed to confirm the expression levels of the hub genes in HCC cells and tissue. RESULTS: A total of 95 DEGs were screened. Results of the GO analysis revealed that DEGs were primarily involved in platelet degranulation, cytoplasm, and protein binding. Results of the KEGG analysis indicated that DEGs were primarily enriched in focal adhesion. Five genes, namely, myosin light chain kinase (MYLK), interleukin 1 beta (IL1B), phospholipase D1 (PLD1), cortactin (CTTN), and moesin (MSN), were identified as hub genes. A search in the CCLE and HPA database showed that the expression levels of these hub genes were remarkably increased in the HCC samples. Survival analysis revealed that the overexpression of MYLK, IL1B, and PLD1 may have a significant effect on HCC survival. The aberrant high expression levels of MYLK, IL1B, and PLD1 strongly indicated worse prognosis in patients with HCC. CONCLUSIONS: The identified hub genes may be closely linked with HCC tumorigenicity and may act as potentially useful biomarkers for the prognostic prediction of HCC in PBMC samples.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/sangue , Protocolos Clínicos , Biomarcadores Tumorais/sangue , Análise por Conglomerados , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Leucócitos Mononucleares , Neoplasias Hepáticas/sangue , Metanálise como Assunto , Prognóstico , Mapas de Interação de Proteínas/genética , Análise de Sobrevida , Revisões Sistemáticas como Assunto
5.
Cancer Sci ; 112(3): 1275-1288, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33426736

RESUMO

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death. High recurrence rates after curative resection and the lack of specific biomarkers for intrahepatic metastases are major clinical problems. Recently, exosomal microRNAs (miRNAs) have been reported to have a role in the formation of the pre-metastatic niche and as promising biomarkers in patients with malignancy. Here we aimed to clarify the molecular mechanisms of intrahepatic metastasis and to identify a novel biomarker miRNA in patients with HCC. A highly intrahepatic metastatic cell line (HuH-7M) was established by in vivo selection. HuH-7M showed increased proliferative ability and suppression of apoptosis and anoikis. HuH-7M and the parental cell (HuH-7P) showed the similar expression of epithelial-mesenchymal transition markers and cancer stem cell markers. In vivo, mice treated with exosomes derived from HuH-7M showed increased tumorigenesis of liver metastases. Exosomes from HuH-7M downregulated endothelial cell expression of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 (ZO-1) in non-cancerous regions of liver and increased the permeability of FITC-dextran through the monolayer of endothelial cells. The miRNAs (miR-638, miR-663a, miR-3648, and miR-4258) could attenuate endothelial junction integrity by inhibiting VE-cadherin and ZO-1 expression. In patients with HCC, higher serum exosomal miR-638 expression was associated with tumor recurrence. In conclusion, the miRNAs secreted from a highly metastatic cancer cell can promote vascular permeability via downregulation of endothelial expression of VE-cadherin and ZO-1. Serum exosomal miR-638 expression holds potential for serving as a significant and independent prognostic marker in HCC.


Assuntos
Antígenos CD/genética , Biomarcadores Tumorais/metabolismo , Caderinas/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Recidiva Local de Neoplasia/diagnóstico , Proteína da Zônula de Oclusão-1/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Células Endoteliais/patologia , Transição Epitelial-Mesenquimal/genética , Exossomos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatectomia , Células Endoteliais da Veia Umbilical Humana , Humanos , Fígado/citologia , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Camundongos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Período Pré-Operatório
6.
BMC Infect Dis ; 21(1): 56, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435880

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression. METHODS: The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays. RESULTS: We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment. CONCLUSION: Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.


Assuntos
Amigdalina/farmacologia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Progressão da Doença , Hepatite B/complicações , Janus Quinase 2/metabolismo , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Idoso , Amigdalina/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Citocinas/metabolismo , Feminino , Células Hep G2 , Hepatite B/virologia , Vírus da Hepatite B/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/metabolismo , Linfócitos T/virologia
7.
ACS Appl Mater Interfaces ; 13(1): 1914-1920, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33378159

RESUMO

Graphdiyne (GD) is a new kind of carbon nanomaterial which has carbon-carbon triple bonds to form a layered structure. Here, we report the application of GD as the matrix for small molecule analysis in laser desorption ionization mass spectrometry (LDI MS). The GD matrix displayed two advantages: little background in the low mass range and good molecular ion signal in negative ion mode for many small molecules, e.g., fatty acids, amino acids, peptides, and drugs can be obtained in negative ion mode. By comparing the signal intensity of tetraphenylborate and juglone with and without GD existing, it was found that GD can enhance both of the desorption efficiency and ionization efficiency in LDI. Through analysis of the serum samples from liver cancer patients and healthy people, the GD-assisted LDI MS results showed that fatty acids could be used as potential biomarkers for the early diagnosis of liver cancer.


Assuntos
Aminoácidos/análise , Ácidos Graxos/sangue , Grafite/química , Compostos Orgânicos/análise , Preparações Farmacêuticas/análise , Biomarcadores Tumorais/sangue , Humanos , Limite de Detecção , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
8.
Clin Biochem ; 89: 44-50, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33309517

RESUMO

OBJECTIVES: The study compared the diagnostic efficiency of serum oligosaccharide chain (G-test) and alpha-fetoprotein (AFP) for hepatitis B-related hepatocellular carcinoma (HCC). METHODS: Serum samples from 100 patients (divided into five groups of 20 each, namely the hepatitis, liver cirrhosis, liver cancer, health, and interference groups) who were admitted to the Second Affiliated Hospital of Nanchang University from October 2019 to January 2020 were collected, and the levels of G-test and AFP were determined. The sensitivity and specificity of the two indicators were compared, and the receiver operating characteristic curve of the subjects was drawn to evaluate the diagnostic values of G-test and AFP for HCC. RESULTS: The diagnostic ability of G-test (area under the curve [AUC]: 0.88 ± 0.05) was better than that of AFP (AUC: 0.76 ± 0.05). When G-test and AFP were combined for detection, the AUC was larger than that of either indicator. The G-test was superior to AFP in the differential diagnosis of early HCC and cirrhosis. A combination of the two indicators (AUC: 0.769 ± 0.05) significantly improved the diagnostic rate for early HCC, indicating that G-test and AFP complemented each other. CONCLUSION: G-test was better than AFP for screening HCC in patients with chronic hepatitis B and cirrhosis. The combination of the two further improved the diagnostic rate of hepatitis B-related liver cancer. The G-test improves the screening rate of early HCC in patients with cirrhosis. Therefore, these markers are of great clinical significance and can improve the sensitivity of HCC detection and reduce missed diagnosis rates.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Vírus da Hepatite B/isolamento & purificação , Hepatite B/complicações , Neoplasias Hepáticas/diagnóstico , Oligossacarídeos/sangue , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Feminino , Hepatite B/virologia , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
9.
Int J Mol Sci ; 21(24)2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33352757

RESUMO

Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. It was upregulated in liver cancer tissues of HBx-tg mouse as well as human HCC tissues. Over-expressed ATIC was also secreted extracellularly via the cancer-derived exosomes, which might cause auto-immune responses. The cyclic peptide mimotope with a high affinity to anti-ATIC autoantibody, CLPSWFHRC, distinguishes between serum samples from HCC patients and healthy subjects with 70.83% sensitivity, 90.68% specificity (AUC = 0.87). However, the recombinant human ATIC protein showed a low affinity to anti-ATIC autoantibody, which may be incompatible as a capture antigen for serum TA autoantibody. This study indicates that anti-ATIC autoantibody can be a potential HCC-associated serum biomarker and suggests that autoantibody biomarker's efficiency can be improved by using antigenic mimicry to native antigens present in vivo.


Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Epitopos/imunologia , Hidroximetil e Formil Transferases/imunologia , Neoplasias Hepáticas/diagnóstico , Complexos Multienzimáticos/imunologia , Nucleotídeo Desaminases/imunologia , Peptídeos Cíclicos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Autoanticorpos/imunologia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/imunologia , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/imunologia , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Biblioteca de Peptídeos , Prognóstico , Adulto Jovem
10.
Medicine (Baltimore) ; 99(40): e22242, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019399

RESUMO

BACKGROUND: To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC). METHODS: Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis. RESULTS: Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57-0.63), 0.95 (95%CI = 0.93-0.96), 0.36 (95%CI = 0.28-0.48), 11.64 (95%CI = 5.85-23.14), and 38.94 (95%CI = 18.33-82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55-3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89-4.86; P < .01). CONCLUSION: CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais , Carcinoma Hepatocelular/sangue , Contagem de Células , Humanos , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia , Células Neoplásicas Circulantes/patologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Sensibilidade e Especificidade , Análise de Sobrevida
11.
Zhonghua Wai Ke Za Zhi ; 58(10): 776-781, 2020 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-32993265

RESUMO

Objective: To examine the value of serum protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) detection in the early diagnosis and surveillance of hepatocellular carcinoma (HCC). Methods: The clinical data of 215 patients with HCC admitted to Department of Hepatobiliary-Pancreatic Surgery of China-Japan Union Hospital of Jilin University from October 2017 to May 2018 were analyzed retrospectively. There were 172 males and 43 females, aged of (59.0±9.3) years old (range 34 to 86 years old). In addition, there were 85 non HCC patients were enrolled in the control group, 42 males and 43 females, aged (54.2±11.3) years old (range 22 to 80 years old). The blood sample of 3 ml was drawn from the elbow vein at 6∶00 am on the next day of admission, and then was kept in low temperature away from light, and sent for PIVKA-Ⅱ detection on the same day. The positive value of AFP was ≥20 µg/L and PIVKA-Ⅱ was ≥32 AU/L. The data were analyzed statistically by χ(2) test, t test or rank sum test. The correlation between AFP, PIVKA-Ⅱ and tumor maximum diameter was analyzed by linear regression. Results: The sensitivity of PIVKA-Ⅱ detection only for the diagnosis of HCC in all stages was significantly higher than AFP or equivalent to AFP, the overall sensitivity of PIVKA-Ⅱ and AFP was 85.1% and 52.1%, respectively. But the specificity of PIVKA-Ⅱ was lower than that of AFP, they were 78.8% and 96.5%, respectively. In particularly, in the earlier stage of HCC (Ⅰa) , the sensitivity of PIVAK-Ⅱ to HCC was 64.5%, while the AFP was only 26.3%. Combined detection of PIVKA-Ⅱ and AFP significantly improved the diagnostic rate of HCC to 88.4%, and the specificity to 76.5%. Moreover, there was a positive correlation between PIVKA-Ⅱ level and the maximum tumor diameter (r(2)=0.587, P<0.05), but there was no correlation between the AFP level and the maximum tumor diameter (r(2)=0.296, P>0.05). The positive rate of PIVKA-Ⅱ in the diagnosis of HCC with vascular invasion was also significantly higher than that of AFP (P<0.01) . Conclusions: PIVKA-Ⅱ can be used as a serological marker for HCC screening and diagnosis. In particular, PIVKA-Ⅱ detection was significantly sensitive than AFP in the earlier stage of HCC. Combined detection of PIVKA-Ⅱ and AFP can effectively improve the diagnostic rate of HCC in all stages. The significant elevation of PIVKA-Ⅱ is also helpful to determine the tumor aggressiveness, vascular invasion and prognosis of HCC patients.


Assuntos
Biomarcadores/sangue , Carcinoma Hepatocelular , Neoplasias Hepáticas , Precursores de Proteínas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Protrombina , Estudos Retrospectivos , Adulto Jovem , alfa-Fetoproteínas/análise
12.
Nat Commun ; 11(1): 4489, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895384

RESUMO

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/genética , Neoplasias Hepáticas/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Química Click/instrumentação , Química Click/métodos , Química Computacional , Simulação por Computador , Diagnóstico Diferencial , Dimetilpolisiloxanos/química , Progressão da Doença , Detecção Precoce de Câncer/instrumentação , Feminino , Células Hep G2 , Humanos , Dispositivos Lab-On-A-Chip , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pessoa de Meia-Idade , Nanoestruturas/química , Nanofios/química , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
13.
Oncology ; 98(11): 779-786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877911

RESUMO

BACKGROUND AND AIMS: Lenvatinib is an oral anticancer drug for patients with unresectable advanced hepatocellular carcinoma (HCC). We evaluated whether a reduction in tumor stain at 2 weeks after lenvatinib treatment in patients with unresectable HCC is a predictor of early treatment efficacy at 12 weeks. PATIENTS AND METHODS: Of the 23 patients who initiated lenvatinib treatment between April 2018 and January 2019, treatment efficacy was measured in 15 patients for more than 12 weeks after treatment. Changes in tumor stain, tumor size on contrast-enhanced computed tomography (CT), and serum levels of tumor markers were evaluated 2 weeks after lenvatinib treatment. Therapeutic efficacy was assessed by tumor stain and tumor size by contrast-enhanced CT within the first 12 weeks, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. RESULTS: At 12 weeks, efficacy evaluation of 15 patients revealed that 11 of them experienced partial responses, for a response rate of 73.3%. In the first 2 weeks, 13 patients (86.7%) experienced a decreased tumor stain, including 10 responders (90.9%) and 3 non-responders (75.0%). All patients in the non-responder group had required a lenvatinib dose reduction due to adverse events within 12 weeks. On contrast-enhanced CT, the change rate of tumor stain to HCC at 2 weeks after treatment was <0.8 among 10 responders (90.9%) and 1 non-responder (25.0%; p = 0.033). No significant differences between responders and non-responders were observed with regard to most characteristics at baseline and at 2 weeks after treatment initiation. However, significant differences were observed between groups in the presence or absence of a dose suspension period, the presence or absence of lenvatinib dose reduction from the maximum value during the first 2 weeks, and decreased tumor stain at 2 weeks after treatment initiation. CONCLUSION: Reduction in tumor stain at 2 weeks after lenvatinib treatment may be an early biomarker of efficacy at 12 weeks in patients with unresectable HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Precursores de Proteínas/sangue , Protrombina , Critérios de Avaliação de Resposta em Tumores Sólidos , Coloração e Rotulagem/métodos , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/metabolismo
14.
PLoS One ; 15(8): e0236569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756596

RESUMO

BACKGROUND: The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with colorectal liver metastases. METHODS: Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. RESULTS: Patients with 2-5 elevated biomarkers were at an increased risk of relapse compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1-1.72) or postoperatively (HR 1.54, 95% CI 1.23-1.92). Patients with 2-5 elevated biomarkers were also at an increased risk of death compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39-2.24) or postoperatively (HR 1.83, 95% CI 1.44-2.33). CONCLUSION: The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Carcinoembrionário/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Hepatectomia , Humanos , Interleucina-6/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Intervalo Livre de Progressão
15.
Int J Nanomedicine ; 15: 4933-4941, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764926

RESUMO

Purpose: The aim of this study was to develop an avidin-modified macromolecular lipid magnetic sphere and its application in differential diagnosis of liver disease and liver cancer. Materials and Methods: Lectin-modified macromolecular lipid magnetic spheres were prepared by thin-film hydration method using lentil lectin derivatives (LCA-HQ) and cholesterol as raw materials. Alpha-fetoprotein variants (AFP-L3) in serum from healthy people, liver disease and liver cancer patients were isolated using the prepared lectin-modified macromolecular lipid magnetic spheres, and alpha-fetoprotein (AFP) and AFP-L3 were detected by fully automatic time-resolved fluorescence immunoassay. Results: The lectin polymer lipid magnetic sphere prepared in this study was superparamagnetic and encapsulated by a lectin derivative. There was no significant difference in the recovery rate of AFP-L3 between avidin magnetic ball-automatic time-resolved fluorescence immunoassay and manual micro-affinity column method (p>0.05). We found that AFP-L3 can be used as a differential indicator between liver cancer and liver disease. The positive rate of AFP and AFP-L3 in liver cancer patients was higher than that in healthy people and liver disease patients (p<0.001). The AUC (95% CI) of AFP and AFP-L3 were 0.743 ± 0.031 and 0.850 ± 0.024, respectively. AFP-L3 AUC value is greater than AFP; therefore, AFP-L3 distinguishes liver cancer more accurately, and the difference is statistically different, p<0.05. Conclusion: We proposed a novel method for integration of the lectin polymer lipid magnetic spheres and time-resolved fluorescence immunoassay that enables simple, accurate and rapid determination of AFP-L3 in clinical samples. To be noted, fully automatic time-resolved fluorescence immunoassay compared with the commonly used techniques in clinical practice, the measurement procedure is simple and is expected to be used for the detection and accurate diagnosis of liver cancer.


Assuntos
Fluorescência , Lipossomos/química , Neoplasias Hepáticas/diagnóstico , Mutação , Polímeros/química , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismo , Adulto , Área Sob a Curva , Automação , Biomarcadores Tumorais/sangue , Feminino , Humanos , Imunoensaio/métodos , Neoplasias Hepáticas/sangue , Imãs/química , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
16.
Medicine (Baltimore) ; 99(31): e21210, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756098

RESUMO

RATIONALE: Procalcitonin (PCT) has been identified as a tumor biomarker in medullary thyroid carcinoma. Other neuroendocrine carcinomas with elevated PCT levels are relatively rare, and are mainly reported in the lung, digestive tract, and pancreas. No studies in the literature have reported a case of primary hepatic carcinoma complicated with unexpectedly elevated PCT levels. PATIENT CONCERNS: A 78-year-old man with persistent fatigue and mild fever was complicated with an extremely high PCT level. Radiological examination revealed a single hypodense lesion in the left lobe of the liver with a "rapid enhancement and rapid washout" pattern. Pathological analysis showed a poorly differentiated neuroendocrine carcinoma (grade 3) with multiple genetic mutations. DIAGNOSIS: Primary hepatic neuroendocrine carcinoma. INTERVENTIONS: The patient received antibiotic therapy and subsequent transcatheter hepatic arterial chemoembolization; a PCT assessment and computed tomography were performed during the follow-up. OUTCOMES: The PCT level did not decline after antibiotic therapy but greatly declined in response to effective transcatheter hepatic arterial chemoembolization. The patient survived and is still being followed up. LESSONS: An extremely elevated PCT level may raise a suspicion of a neuroendocrine carcinoma and plays an indicative role as a biomarker during therapy.


Assuntos
Carcinoma Neuroendócrino/diagnóstico , Neoplasias Hepáticas/diagnóstico , Pró-Calcitonina/sangue , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/terapia , Quimioembolização Terapêutica , Diagnóstico Diferencial , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Masculino , Tomografia Computadorizada por Raios X
17.
PLoS One ; 15(8): e0237370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857769

RESUMO

BACKGROUND: Copper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib. METHODS: We enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy. RESULTS: The serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratio≥0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratio<0.999 (45.3 vs. 30.1 months, p<0.001). MT was significantly correlated with the Cu/Zn ratio and increased after the administration of lenvatinib. Using multivariate Cox regression analyses, it was determined that the Cu/Zn ratio (hazard ratio [HR]: 1.442, p = 0.008), alpha-fetoprotein (HR: 1.000, p<0.001) and BCLC stage (HR: 2.087, p<0.001) were independent predictors of survival. CONCLUSIONS: The Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Cobre/sangue , Neoplasias Hepáticas/sangue , Metalotioneína/sangue , Zinco/sangue , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico
18.
Anticancer Res ; 40(7): 4173-4182, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620667

RESUMO

BACKGROUND/AIM: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of cancers. Sorafenib, an oral multi-target TKI, improves the median overall survival time in patients with hepatocellular carcinoma (HCC). It also inhibits the absorption of carnitine by down-regulating the human organic cationic transporter OCTN2 located largely in the small intestinal mucosa and skeletal muscle. The aim of the study was to determine, by assessing carnitine metabolism, whether sarcopenia is induced in patients with HCC who are receiving sorafenib. PATIENTS AND METHODS: This retrospective study included 110 adult Japanese patients with liver cirrhosis and HCC who received sorafenib. Sorafenib was administered at a dose of 200-800 mg/day for 4 weeks. Blood samples were collected before and after treatment, and serum carnitine fraction and myostatin levels were measured. Cross-sectional areas (cm2) of the skeletal muscles at the third lumbar vertebra level were determined by manually outlining computed tomography images before and after treatment. The cross-sectional areas were normalized for height [skeletal muscle index (SMI), cm2/m2]. RESULTS: Patients were allocated to two groups according to Child-Pugh (CP) class; 81 had CP-A liver function, and 29 had CP-B. SMI after treatment was significantly lower than that before treatment in both groups. Serum levels of total carnitine and free carnitine after treatment were significantly lower than those before treatment in both groups. There were no differences in serum levels of myostatin before and after treatment in either group. CONCLUSION: Sorafenib might decrease serum levels of carnitine by inhibiting carnitine absorption. Decreasing of serum levels of carnitine might lead to presarcopenia.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carnitina/sangue , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Sarcopenia/induzido quimicamente , Sorafenibe/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carnitina/metabolismo , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade
19.
Oncol Rep ; 44(4): 1727-1735, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32700752

RESUMO

Hepatocellular carcinoma (HCC) is a common hypervascular tumor disease. Endothelial cells, as a crucial component of the tumor microenvironment, have been reported to participate in angiogenesis and influence the development of tumors, including HCC. Recent studies have demonstrated that circulating RNAs (circRNAs) participate in the functional regulation of endothelial cells. However, the expression and function of circRNAs in endothelial cells under the HCC microenvironment is still unclear. In the present study, we analyzed the expression profiles and investigated the role of circRNAs in human umbilical vein endothelial cells (HUVECs) co­cultured with human primary hepatoma cells. Based on an RNA­sequencing assay, we screened 19 significantly downregulated circRNAs in HUVECs under an HCC microenvironment. Subsequently, we validated the expression of the candidate circRNAs using RT­qPCR, and selected two of the most downregulated circRNAs among them, circ_4911 and circ_4302. Next, through circRNA overexpression experiments, we demonstrated that overexpression of circ_4911 and circ_4302 both inhibited the proliferation and migration of HUVECs, and arrested cells at the GO/G1 stage, while promoting adhesion. Overall, in the present study, we identified the roles of circ_4911 and circ_4302 in regulating functions of HUVECs under an HCC microenvironment.


Assuntos
Carcinoma Hepatocelular/genética , Ácidos Nucleicos Livres/genética , Endotélio Vascular/patologia , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Ácidos Nucleicos Livres/sangue , Técnicas de Cocultura , Endotélio Vascular/metabolismo , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA , Células Tumorais Cultivadas , Microambiente Tumoral
20.
PLoS One ; 15(5): e0232449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379785

RESUMO

BACKGROUND AND AIMS: The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. METHODS: This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). RESULTS: A PNI cut-off value of 31.3 was established using the ROC analysis. In the training cohort, the median OS was 14.8 months (95% CI 12-76.3) and 6.8 months (95% CI 2.7-24.6) for patients with a high (>31.3) and low (<31.3) PNI, respectively. At both the univariate and the multivariate analysis, low PNI value (p = 0.0004), a 1-unit increase of aspartate aminotransferase (p = 0.0001), and age > 70 years (p< 0.0038) were independent prognostic factors for OS. By performing the same multivariate analysis of the training cohort, the PNI <31.3 versus >31.3 was found to be an independent prognostic factor for predicting OS in all the three validation cohorts. CONCLUSIONS: PNI represents a prognostic tool in advanced HCC treated with first-line Sorafenib. It is readily available and low-cost, and it could be implemented in clinical practice in patients with HCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Avaliação Nutricional , Sorafenibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Albumina Sérica/metabolismo
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