title: Neighbor of Punc E11, a novel oncofetal marker for hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is the 5th common malignancy worldwide, but established markers fail to detect up to one third of HCC. We have recently identified Neighbor of Punc E11 (Nope) as a surface marker for murine fetal liver stem cells. Similar to commonly used HCC markers such as α-Fetoprotein (Afp) and Glypican-3 (Gpc-3), we here establish Nope as an oncofetal marker of murine and human HCC and investigate its specific expression in hepatoma cell lines and primary HCC. Murine and human hepatoma cell lines and Cre-inducible SV40 T-antigen transgenic mice (Alb-SV40TAg(ind) ) were analyzed for Nope expression in comparison to common HCC markers by quantitative RT-PCR, Western blot analyses and immunohistochemistry. Nope expression in primary human HCC was investigated using Oncomine Microarray database. Nope expression was elevated in 8 of 10 investigated murine and human hepatoma cell lines and in all tumors of our oncogenic mouse model but remained undetectable in normal liver and at preneoplastic stages of murine hepatocarcinogenesis. Furthermore, a significant induction of Nope was detected in primary human cancers compared to corresponding normal or cirrhotic tissue. Nope expression in tumor specimens and murine cell lines correlated closely with expression levels of Gpc-3, whereas expression levels of Afp showed high variations. In conclusion, we identified Nope as a novel oncofetal surface marker for murine and human HCC. Nope is specifically expressed by epithelial tumor cells but not in preneoplastic stages and is a promising marker for clinical application because of its high detection rate in Afp-positive and Afp-negative tumors.
authors.affiliation: Department of Gastroenterology and Hepatology, University of Cologne, Germany.
authors.forename: Jens Uwe
authors.initials: JU
authors.lastname: Marquardt
authors.forename: Maria
authors.initials: M
authors.lastname: Quasdorff
authors.forename: Heike
authors.initials: H
authors.lastname: Varnholt
authors.forename: Harald-Morten
authors.initials: HM
authors.lastname: Curth
authors.forename: Senait
authors.initials: S
authors.lastname: Mesghenna
authors.forename: Ulrike
authors.initials: U
authors.lastname: Protzer
authors.forename: Tobias
authors.initials: T
authors.lastname: Goeser
authors.forename: Dirk
authors.initials: D
authors.lastname: Nierhoff
mesh_terms: D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; C558360:IGDCC4 protein, human; D007136:Immunoglobulins; D009419:Nerve Tissue Proteins; C408892:Nope protein, mouse