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Verfasst von:Hennig, Alexander [VerfasserIn]   i
 Weitz, Jürgen [VerfasserIn]   i
 Stange, Daniel Eduard [VerfasserIn]   i
 Welsch, Thilo [VerfasserIn]   i
Titel:CFTR expression analysis for subtyping of human pancreatic cancer organoids
Verf.angabe:Alexander Hennig, Laura Wolf, Beatrix Jahnke, Heike Polster, Therese Seidlitz, Kristin Werner, Daniela E. Aust, Jochen Hampe, Marius Distler, Jürgen Weitz, Daniel E. Stange, Thilo Welsch
E-Jahr:2019
Jahr:2 May 2019
Umfang:8 S.
Fussnoten:Gesehen am 26.08.2019
Titel Quelle:Enthalten in: Stem cells international
Ort Quelle:London [u.a.] : Sage-Hindawi, 2010
Jahr Quelle:2019
Band/Heft Quelle:(2019) Artikel-Nummer 1024614, 8 Seiten
ISSN Quelle:1687-9678
Abstract:Background: Organoid cultures of human pancreatic ductal adenocarcinoma (PDAC) have become a promising tool for tumor subtyping and individualized chemosensitivity testing. PDACs have recently been grouped into different molecular subtypes with clinical impact based on cytokeratin-81 (KRT81) and hepatocyte nuclear factor 1A (HNF1A). However, a suitable antibody for HNF1A is currently unavailable. The present study is aimed at establishing subtyping in PDAC organoids using an alternative marker. - Methods: A PDAC organoid biobank was generated from human primary tumor samples containing 22 lines. Immunofluorescence staining was established and done for 10 organoid lines for cystic fibrosis transmembrane conductance regulator (CFTR) and KRT81. Quantitative real-time PCR (qPCR) was performed for CFTR and HNF1A. A chemotherapeutic drug response analysis was done using gemcitabine, 5-FU, oxaliplatin, and irinotecan. - Results: A biobank of patient-derived PDAC organoids was established. The efficiency was 71% (22/31) with 68% for surgical resections and 83% for fine needle aspirations. Organoids could be categorized into the established quasimesenchymal, exocrine-like, and classical subtypes based on KRT81 and CFTR immunoreactivity. CFTR protein expression was confirmed on the transcript level. CFTR and HNF1A transcript expression levels positively correlated (n = 10; r = 0.927; p = 0.001). PDAC subtypes of the primary tumors and the corresponding organoid lines were identical for most of the cases analyzed (6/7). Treatment with chemotherapeutic drugs revealed tendencies but no significant differences regarding drug responses. - Conclusions: Human PDAC organoids can be classified into known subtypes based on KRT81 and CFTR immunoreactivity. CFTR and HNF1A mRNA levels correlated well. Furthermore, subtype-specific immunoreactivity matched well between PDAC organoids and the respective primary tumor tissue. Subtyping of human PDACs using CFTR might constitute an alternative to HNF1A and should be further investigated.
DOI:doi:10.1155/2019/1024614
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.1155/2019/1024614
 DOI: https://doi.org/10.1155/2019/1024614
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1672098017
Verknüpfungen:→ Zeitschrift

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