Universität zu Köln

Nestler, Tim, Kremer, Lara, von Brandenstein, Melanie, Wittersheim, Maike, Paffenholz, Pia, Wagener-Ryczek, Svenja, Quaas, Alexander, Hellmich, Martin, Mueller, Stefan, Pfister, David, Odenthal, Margarete and Heidenreich, Axel (2023). Differentially expressed messenger RNA/proteins can distinguish teratoma from necrosis in postchemotherapy retroperitoneal lymph node dissection (pcRPLND) tissue. Cancer, 129 (4). S. 634 - 643. HOBOKEN: WILEY. ISSN 1097-0142

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Abstract

BackgroundBefore postchemotherapy retroperitoneal lymph node dissection (pcRPLND), in patients with metastasized germ cell tumors (GCTs), those harboring necrosis (NEC) cannot be distinguished from those who have teratoma (TER), resulting in relevant overtreatment, whereas microRNA-371a-3p may be predictive for viable GCT. The purpose of this study was to explore messenger RNA (mRNA) and proteins to distinguish TER from NEC in pcRPLND tissue. MethodsThe discovery cohort consisted in total of 48 patients, including 16 each with TER, viable GCT, and NEC. Representative areas were microdissected. A NanoString panel and proteomics were used to analyze 770 genes and >5000 proteins. The most significantly and differentially expressed combination of both parameters, mRNA and its associated protein, between TER and NEC was validated using immunohistochemistry (IHC) in an independent validation cohort comprising 66 patients who were not part of the discovery cohort. ResultsThe authors observed that anterior gradient protein 2 homolog (AGR2) and keratin, type I cytoskeletal 19 (KRT19) were significantly differentially expressed in TER versus NEC in mRNA and protein analyses (proteomics). The technical validation using IHC was successful in the same patients. These proteins were further validated by IHC in the independent patient cohort and exhibited significantly higher levels in TER versus NEC (p < .0001; area under the curve, 1.0; sensitivity and specificity, 100% each). ConclusionsThe current study demonstrated that KRT19 and AGR2 mRNA and protein are overexpressed in TER versus NEC in pcRPLND tissue and might serve as a future diagnostic target to detect TER, for instance, by functional imaging, to avoid overtreatment. Plain language summary The proteins and the corresponding genes called AGR2 and KRT19 can differentiate between teratoma and necrosis in remaining tumor masses after chemotherapy in patients who have metastasized testicular cancer.This may be a way to improve presurgical diagnostics and to reduce the current overtreatment of patients with necrosis only, who could be treated sufficiently by surveillance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nestler, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Kremer, Lara UNSPECIFIED UNSPECIFIED UNSPECIFIED von Brandenstein, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittersheim, Maike UNSPECIFIED UNSPECIFIED UNSPECIFIED Paffenholz, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener-Ryczek, Svenja UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellmich, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, Margarete UNSPECIFIED UNSPECIFIED UNSPECIFIED Heidenreich, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-672474
DOI:	10.1002/cncr.34571
Journal or Publication Title:	Cancer
Volume:	129
Number:	4
Page Range:	S. 634 - 643
Date:	2023
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0142
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL; CLASSIFICATION; IDENTIFY; SYSTEM; TUMORS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67247