First evaluation of Neighbor of Punc E11 (NOPE) as a novel marker in human hepatocellular carcinoma

Article type: Research Article

Authors: Zweerink, Susanne^a | Mesghenna, Senait^b | Mueck, Vera^a | Schulte, Sigrid^a | Kuetting, Fabian^a | Quaas, Alexander^{c; d} | Goeser, Tobias^a | Nierhoff, Dirk^{a; *}

Affiliations: [a] Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany | [b] Department of Internal Medicine, Donau-Ries Clinic Donauworth, Donauworth, Germany | [c] Institute of Pathology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany | [d] Gastrointestinal Cancer Group Cologne (GCGC), Cologne, Germany

Correspondence: [*] Corresponding author: Dirk Nierhoff, Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital of Cologne, Kerpener Str. 62 50937 Cologne, Germany. Tel.: +49 221 478 7280; Fax: +49 221 478 6758; E-mail: dirk.nierhoff@uk-koeln.de.

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide and the search for clinically useful biomarkers is ongoing. Neighbor of Punc E11 (NOPE) is an established biomarker of murine HCC that remains undetectable in normal liver and at preneoplastic stages. OBJECTIVE: The aim of our study was to evaluate the presence of NOPE in human HCC. METHODS: Histologically confirmed HCC and corresponding non-tumor liver samples from 20 patients were analyzed for expression of NOPE using qRT-PCR and mRNA-in-situ technology in a conserved tissue context. RESULTS: In our cohort, 30% of HCC samples were expressing NOPE which proved particularly useful in non-cirrhotic HCC samples with up to 155-fold higher expression than in adult liver. Using mRNA-in-situ technology, NOPE was clearly identified within epithelial tumor cells of NOPE positive human HCCs. In our analyzed cohort, the combination of AFP with NOPE did not reach more than 40% sensitivity while GPC-3 and NOPE were complementary to each other reaching a combined sensitivity of 85.7%. CONCLUSIONS: This is the first characterization of NOPE as a potential biomarker for human HCC. Our results underline the value of NOPE as a complementing biomarker for human HCC.

Keywords: Human HCC, biomarker, IGDCC4, mRNA-in situ technology, AFP, GPC-3

DOI: 10.3233/CBM-190819

Journal: Cancer Biomarkers, vol. 30, no. 1, pp. 75-83, 2021