BACKGROUND Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However...BACKGROUND Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate(GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels.AIM To survey the literature to capture the involvement of genes regulating core Nlinked fucosylation in hepatocellular carcinoma METHODS The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma(LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal.RESULTS A total of 27 citations involving one or more of the core fucosylation-related genes(FPGT, FUK, FUT8, GMDS, SLC35 C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the371 patients with liver cancer in the LIHC dataset to identify the frequency of m RNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to moresamples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the de novo synthesis pathway, GMDS(27 samples) and TSTA3(78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples.CONCLUSION Amplification of genes involved in the de novo pathway for generation of GDPfucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.展开更多
Chromosome 1q often has been observed to be amplified in hepatocellular carcinoma.This review summarizes literature reports of multiple genes that have been proposed as possible 1q amplification drivers.These largely ...Chromosome 1q often has been observed to be amplified in hepatocellular carcinoma.This review summarizes literature reports of multiple genes that have been proposed as possible 1q amplification drivers.These largely fall within 1q21-1q23.In addition,publicly available copy number alteration data from The Cancer Genome Atlas project were used to identify additional candidate genes involved in carcinogenesis.The most frequent location for gene amplification was 1q22,consistent with the results of the literature search.The genes TPM3 and NUF2 were found to be candidates whose amplification and/or mRNA up-regulation was most highly associated with poorer hepatocellular carcinoma outcomes.展开更多
文摘BACKGROUND Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate(GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels.AIM To survey the literature to capture the involvement of genes regulating core Nlinked fucosylation in hepatocellular carcinoma METHODS The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma(LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal.RESULTS A total of 27 citations involving one or more of the core fucosylation-related genes(FPGT, FUK, FUT8, GMDS, SLC35 C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the371 patients with liver cancer in the LIHC dataset to identify the frequency of m RNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to moresamples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the de novo synthesis pathway, GMDS(27 samples) and TSTA3(78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples.CONCLUSION Amplification of genes involved in the de novo pathway for generation of GDPfucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.
文摘Chromosome 1q often has been observed to be amplified in hepatocellular carcinoma.This review summarizes literature reports of multiple genes that have been proposed as possible 1q amplification drivers.These largely fall within 1q21-1q23.In addition,publicly available copy number alteration data from The Cancer Genome Atlas project were used to identify additional candidate genes involved in carcinogenesis.The most frequent location for gene amplification was 1q22,consistent with the results of the literature search.The genes TPM3 and NUF2 were found to be candidates whose amplification and/or mRNA up-regulation was most highly associated with poorer hepatocellular carcinoma outcomes.
