Dataset Information

Alpha-L-Fucosidase Serves as a Prognostic Indicator for Intrahepatic Cholangiocarcinoma and Inhibits Its Invasion Capacity.

ABSTRACT: Alpha-L-fucosidase (AFU) has been reported to be a predictor of survival in patients with several cancers, but it is unclear whether AFU is associated with prognosis in patients with intrahepatic cholangiocarcinoma (iCCA). In this study, we used receiver operating characteristic (ROC) analysis to generate the cutoff point of AFU for overall survival (OS). The prognostic influence of the AFU level in serum on OS was studied using Kaplan-Meier curves. Moreover, invasion assays and Western blotting were performed to explore the effects of AFU on iCCA invasion in vitro. We found that higher AFU levels (?20.85?U/L) were significantly associated with favorable median OS (44.3 months versus 20.1 months; P = 0.022) in iCCA patients. Cox regression models' analyses showed that the AFU level was an independent predictor for OS (P = 0.006). Moreover, our results revealed that the AFU could impair the invasion capability of the iCCA cells, HuH28, and also downregulated the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. In conclusion, our results indicate that AFU is a significantly favorable prognostic factor in iCCA patients.

SUBMITTER: Shuang Z

PROVIDER: S-EPMC5842738 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Alpha-L-Fucosidase Serves as a Prognostic Indicator for Intrahepatic Cholangiocarcinoma and Inhibits Its Invasion Capacity.

Shuang Zeyu Z Mao Yize Y Lin Guohe G Wang Jun J Huang Xin X Chen Jianlin J Duan Fangting F Li Shengping S

BioMed research international 20180222

Alpha-L-fucosidase (AFU) has been reported to be a predictor of survival in patients with several cancers, but it is unclear whether AFU is associated with prognosis in patients with intrahepatic cholangiocarcinoma (iCCA). In this study, we used receiver operating characteristic (ROC) analysis to generate the cutoff point of AFU for overall survival (OS). The prognostic influence of the AFU level in serum on OS was studied using Kaplan-Meier curves. Moreover, invasion assays and Western blotting ...[more]

PMID: 29682557

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Project description:Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer. It is defined by cholangiocytic differentiation and has poor prognosis. Recently, epigenetic processes have been shown to play an important role in cholangiocarcinogenesis. We performed an integrative analysis on 52 iCCAs using both genetic and epigenetic data with a specific focus on DNA methylation components. We found recurrent isocitrate dehydrogenase 1 (IDH1) and IDH2 (28%) gene mutations, recurrent arm-length copy number alterations (CNAs), and focal alterations such as deletion of 3p21 or amplification of 12q15, which affect BRCA1 Associated Protein 1, polybromo 1, and mouse double minute 2 homolog. DNA methylome analysis revealed excessive hypermethylation of iCCA, affecting primarily the bivalent genomic regions marked with both active and repressive histone modifications. Integrative clustering of genetic and epigenetic data identified four iCCA subgroups with prognostic relevance further designated as IDH, high (H), medium (M), and low (L) alteration groups. The IDH group consisted of all samples with IDH1 or IDH2 mutations and showed, together with the H group, a highly disrupted genome, characterized by frequent deletions of chromosome arms 3p and 6q. Both groups showed excessive hypermethylation with distinct patterns. The M group showed intermediate characteristics regarding both genetic and epigenetic marks, whereas the L group exhibited few methylation changes and mutations and a lack of CNAs. Methylation-based latent component analysis of cell-type composition identified differences among these four groups. Prognosis of the H and M groups was significantly worse than that of the L group. Conclusion: Using an integrative genomic and epigenomic analysis approach, we identified four major iCCA subgroups with widespread genomic and epigenomic differences and prognostic implications. Furthermore, our data suggest differences in the cell-of-origin of the iCCA subtypes.

Dataset Information

Alpha-L-Fucosidase Serves as a Prognostic Indicator for Intrahepatic Cholangiocarcinoma and Inhibits Its Invasion Capacity.

Publications

Alpha-L-Fucosidase Serves as a Prognostic Indicator for Intrahepatic Cholangiocarcinoma and Inhibits Its Invasion Capacity.

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