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http://purl.uniprot.org/citations/25531719http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25531719http://www.w3.org/2000/01/rdf-schema#comment"

Background

The molecular pathomechanisms leading to hepatitis C virus (HCV)-induced hepatocarcinogenesis remain unclear. This study investigated the molecular pathways and key genes underlying HCV-positive hepatocellular carcinoma (HCC) using gene expression profiling.

Methods

Oligonucleotide arrays (Affymetrix HU133A) were used to determine and compare the tissue-specific gene expression profiles in 39 cases of HCV-positive or -negative HCC and non-malignant liver tissue. The expression values of the most overexpressed genes were validated by real-time polymerase chain reaction (RT-PCR).

Results

837 genes or expressed sequence tags (ESTs) were significantly differently expressed in HCV-positive HCC versus healthy tissue: 414 were upregulated and 423 were downregulated (p < 0.05; > 2-fold change in ≥ 70% of the samples). A specific gene expression profile for HCV-positive HCC was obtained using 2-dimensional cluster analysis and was confirmed using supervised neuronal network modeling. The most consistently overexpressed gene coded for serine protease inhibitor Kazal-type 1 (SPINK1)/tumor-associated trypsin inhibitor (TATI) (median fold change, 19.7; significantly overexpressed in 90% of the samples). SPINK1/TATI was coregulated with matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of metalloproteinases (TIMPs)).

Conclusions

Gene expression profiling identified specific dysregulated molecular pathways and SPINK1/TATI as the most overexpressed gene in HCV-positive HCC. These data highlight the importance of SPINK1/TATI as a tumor marker for HCV-induced HCC and may lead to a better understanding of HCV-induced hepatocarcinogenesis."xsd:string
http://purl.uniprot.org/citations/25531719http://purl.org/dc/terms/identifier"doi:10.1159/000369151"xsd:string
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/author"Vogel U."xsd:string
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/author"Scheurlen M."xsd:string
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/author"Hass H.G."xsd:string
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/author"Nehls O."xsd:string
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/author"Jobst J."xsd:string
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/name"Oncol Res Treat"xsd:string
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/pages"732-738"xsd:string
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/title"Overexpression of tumor-associated trypsin inhibitor (SPINK1/TATI) in hepatitis C-associated hepatocellular carcinoma: potential implications for viral hepatocarcinogenesis."xsd:string
http://purl.uniprot.org/citations/25531719http://purl.uniprot.org/core/volume"37"xsd:string
http://purl.uniprot.org/citations/25531719http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25531719
http://purl.uniprot.org/citations/25531719http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25531719
http://purl.uniprot.org/uniprot/#_A2T2X6-mappedCitation-25531719http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25531719
http://purl.uniprot.org/uniprot/#_A2T2X7-mappedCitation-25531719http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25531719
http://purl.uniprot.org/uniprot/#_P00995-mappedCitation-25531719http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25531719
http://purl.uniprot.org/uniprot/A2T2X7http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/25531719
http://purl.uniprot.org/uniprot/P00995http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/25531719
http://purl.uniprot.org/uniprot/A2T2X6http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/25531719