RESUMO
BACKGROUND AND AIMS: Cytokeratin19 positive (CK19+) hepatocellular carcinoma (HCC) is thought to derive from liver progenitor cells (LPC). However, whether peritumoralductular reaction (DR) differs between CK19+ and CK19 negative (CK19-) HCC patients remains unclear. MATERIAL AND METHODS: One hundred and twenty HBV-related HCC patients were enrolled in this study. Clinicopathological variables were collected, and immunohistochemistry staining for CK19, proliferating cell nuclear antigen (PCNA), interleukin-6 (IL-6) and ß-catenin were performed in tumor and peritumor liver tissues. RESULTS: CK19+ HCC patients had higher grade of peritumoral DR and proportion of proliferative DR than the CK19- group. The mean number or the proportion of cytoplasmic ß-catenin+ DR was higher in the CK19+ group than in the CK19- group. Furthermore, there were more patients with nuclear ß-catenin+ peritumoral DR in the CK19+ group as compared to the CK19- group. CONCLUSION: Peritumoral DR was more abundant and proliferative in CK19+ HCC patients, with higher level of nuclear translocation of ß-catenin. However, it is unclear whether peritumoral DR is the cause or result of poor prognosis in these patients.
Assuntos
Ductos Biliares Intra-Hepáticos/química , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/química , Queratina-19/análise , Neoplasias Hepáticas/química , Transporte Ativo do Núcleo Celular , Adulto , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Biópsia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Proliferação de Células , Feminino , Hepatectomia , Humanos , Imuno-Histoquímica , Interleucina-6/análise , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Regulação para Cima , beta Catenina/análiseRESUMO
AIM: The present study aimed to evaluate the changes in the serum N-glycome profiles in chronic hepatitis B (CHB) patients and to assess the role of N-glycome-derived markers in the noninvasive diagnosis of liver fibrosis. MATERIALS AND METHODS: After liver biopsy for pathological grading and staging, 128 CHB patients underwent serum N-glycomic analysis using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) and sensitive markers were screened. RESULTS: Peaks 1, 2, 8 and 10 in the N-glycome profiles could, to some extents, distinguish liver fibrosis at different stages. In addition, the N-glycome-derived marker log(peak2/peak8) possessed the highest diagnostic accuracy. The areas under the receiver operating characteristic (AUROCs) curves of the log(peak2/peak8) were 0.675, 0.736 and 0.754 in the diagnosis of significant fibrosis, advanced fibrosis and early cirrhosis, respectively. In combination with some marker panels (SLFG, S index, Fibrometer, Hui, Forns, APRI and Hepascore), it showed the best diagnostic potency in distinguishing significant fibrosis (SLFG + log[peak2/peak8], AUROC = 0.813) from advanced fibrosis (SLFG + log[peak2/peak8], AUROC = 0.899) and a better diagnostic potency in the identification of early cirrhosis (S index + log[peak2/peak8], AUROC = 0.903, lower than Hui model [AUROC = 0.927]) in the validation cohort. CONCLUSIONS: N-glycomic changes are present in the serum of CHB patients with liver fibrosis, and N-glycan profiling is a noninvasive and effective tool to assess the liver fibrosis, especially in combination with serum marker panels.