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Alpha-1-fucosidase as a prognostic indicator for hepatocellular carcinoma following hepatectomy: a large-scale, long-term study.

ABSTRACT: BACKGROUND: Preoperative alpha-L-fucosidase (AFU) has been used as a diagnostic biomarker for hepatocellular carcinoma (HCC), but its role as a prognostic predictor after partial hepatectomy has not been well defined. The study aimed to investigate the prognostic significance of preoperative serum AFU for HCC patients after hepatic resection. METHODS: A retrospective training data set and a prospective validation data set were used to evaluate the prognosis of HCC after partial hepatectomy. A total of 669 patients with histopathologically confirmed HCC were enrolled. Univariate and multivariate analyses were used to identify the prognostic significance of preoperative serum AFU. RESULTS: The retrospective training data set showed a preoperative AFU>35?u?l(-1) should be used. The prospective validation data set showed preoperative AFU was an independent prognostic factor of overall survival (OS) (P=0.008; hazard ratio: 2.333; 95% confidence interval: 1.249-4.369). Patients with a preoperative AFU>35?u?l(-1) had a lower recurrence-free survival rate and an OS rate than those with AFU?35?u?l(-1), and they have a higher tendency to form macrovascular invasion. Furthermore, the prognostic significance of AFU>35?u?l(-1) could also be applied to patients with alpha-fetoprotein levels of ?400?ng?ml(-1). CONCLUSIONS: Preoperative serum AFU is a prognostic predictor of HCC.

SUBMITTER: Wang K

PROVIDER: S-EPMC3974071 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Alpha-1-fucosidase as a prognostic indicator for hepatocellular carcinoma following hepatectomy: a large-scale, long-term study.

Wang K K Guo W W Li N N Shi J J Zhang C C Lau W Y WY Wu M M Cheng S S

British journal of cancer 20140225 7

<h4>Background</h4>Preoperative alpha-L-fucosidase (AFU) has been used as a diagnostic biomarker for hepatocellular carcinoma (HCC), but its role as a prognostic predictor after partial hepatectomy has not been well defined. The study aimed to investigate the prognostic significance of preoperative serum AFU for HCC patients after hepatic resection.<h4>Methods</h4>A retrospective training data set and a prospective validation data set were used to evaluate the prognosis of HCC after partial hepa ...[more]

PMID: 24569461

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Project description:Hepatocellular carcinoma (HCC) is the most common cause of cancer-related mortality globally. Since the prognosis of advanced HCC patients is extremely poor, the development of novel molecular targets for diagnosis and therapy is urgently required. In the present study, the expression of the melanoma-associated antigen-D2 (MAGE-D2) gene was investigated to determine whether it affects the malignant phenotype of HCC and thus, may serve as a marker of prognosis. Therefore, the expression of MAGE-D2 mRNA and MAGE-D2 protein in nine HCC cell lines and 151 pairs of surgical tissues was analyzed. mRNA expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry was used to compare the clinicopathological parameters of the tumors. A significant difference in the level of MAGE-D2 expression was observed between the normal liver and chronic hepatitis tissues, however, no significant differences were identified among the levels of the chronic hepatitis, cirrhosis and HCC tissues. The expression patterns of the MAGE-D2 protein were consistent with those of its mRNA. The expression levels of MAGE-D2 mRNA in 66 of 151 (44%) patients were higher in the HCC tissues compared with the corresponding non-cancerous tissues. In addition, the disease-specific survival time was significantly shorter for patients with higher levels of MAGE-D2 mRNA expression. Multivariate analysis identified increased expression of MAGE-D2 mRNA as an independent prognostic factor for disease-specific survival (hazard ratio, 2.65; 95% confidence interval, 1.43-4.98; P=0.002). However, increased expression levels of MAGE-D2 mRNA were not significantly associated with other clinicopathological parameters, including extrahepatic recurrence. These results indicated that MAGE-D2 mRNA affects tumor progression and may serve as a prognostic indicator following curative resection. In addition, MAGE-D2 may provide a target for the therapy of HCC.

Project description:BackgroundThis study investigated the prognostic and immunological significance of alpha-L-fucosidase 2 (FUCA2) in hepatocellular cancer (HCC).MethodsThe expression of FUCA2 and its clinical and prognostic values were explored across several databases, namely the University of Alabama Cancer Database, The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, and the Human Protein Atlas. The prognostic relevance of FUCA2 was investigated using Kaplan-Meier curves, nomograms, and Cox analysis. The "limma" package in R was used to identify differentially expressed genes between high and low FUCA2 expression. A protein interaction network was established using the Search Tool for the Retrieval of Interacting Genes (STRING), whereas hub genes and clustering modules were identified using Cytoscape. "clusterProfiler", an R package, was used to examine the potential function of FUCA2. Using gene set enrichment analysis, signaling pathways associated with FUCA2 expression were identified. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), Tumor Immune Estimation Resource (TIMER) 2.0, and Tumor and Immune System Interaction Database (TISIDB) were used to examine immune infiltration and FUCA2 in HCC.ResultsMany datasets indicated that FUCA2 expression is higher in HCC, and that this is related to age and overall survival (OS). With the cutoff value of 50% as the dividing threshold, the patients were divided into a high-FUCA2 expression group (n=167) and a low-FUCA2 expression group (n=168). High levels of FUCA2 expression coincided with decreased OS. FUCA2 expression in HCC was associated with immune infiltrates. The functional mechanisms of FUCA2 depend on signal release, extracellular matrix collagen, and neuroactive ligands and receptors.ConclusionsIn HCC, increased FUCA2 expression is associated with a poor prognosis and immune infiltration. FUCA2 may serve as an immunological and predictive biomarker for HCC.

Dataset Information

Alpha-1-fucosidase as a prognostic indicator for hepatocellular carcinoma following hepatectomy: a large-scale, long-term study.

Publications

Alpha-1-fucosidase as a prognostic indicator for hepatocellular carcinoma following hepatectomy: a large-scale, long-term study.

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