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Status: Bibliographieeintrag

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Verfasst von:Schneider, Felix [VerfasserIn]   i
 Kaczorowski, Adam [VerfasserIn]   i
 Jurcic, Christina [VerfasserIn]   i
 Kirchner, Martina [VerfasserIn]   i
 Schwab, Constantin [VerfasserIn]   i
 Schütz, Viktoria [VerfasserIn]   i
 Görtz, Magdalena [VerfasserIn]   i
 Zschäbitz, Stefanie [VerfasserIn]   i
 Jäger, Dirk [VerfasserIn]   i
 Stenzinger, Albrecht [VerfasserIn]   i
 Hohenfellner, Markus [VerfasserIn]   i
 Duensing, Stefan [VerfasserIn]   i
 Duensing, Anette [VerfasserIn]   i
Titel:Digital spatial profiling identifies the tumor periphery as a highly active biological niche in clear cell renal cell carcinoma
Verf.angabe:Felix Schneider, Adam Kaczorowski, Christina Jurcic, Martina Kirchner, Constantin Schwab, Viktoria Schütz, Magdalena Görtz, Stefanie Zschäbitz, Dirk Jäger, Albrecht Stenzinger, Markus Hohenfellner, Stefan Duensing and Anette Duensing
E-Jahr:2023
Jahr:10 October 2023
Umfang:15 S.
Illustrationen:Illustrationen
Fussnoten:Gesehen am 06.12.2023
Titel Quelle:Enthalten in: Cancers
Ort Quelle:Basel : MDPI, 2009
Jahr Quelle:2023
Band/Heft Quelle:15(2023), 20, Artikel-ID 5050, Seite 1-15
ISSN Quelle:2072-6694
Abstract:Clear cell renal cell carcinoma (ccRCC) is characterized by a high degree of intratumoral heterogeneity (ITH). Besides genomic ITH, there is considerable functional ITH, which encompasses spatial niches with distinct proliferative and signaling activities. The full extent of functional spatial heterogeneity in ccRCC is incompletely understood. In the present study, a total of 17 ccRCC tissue specimens from different sites (primary tumor, n = 11; local recurrence, n = 1; distant metastasis, n = 5) were analyzed using digital spatial profiling (DSP) of protein expression. A total of 128 regions of interest from the tumor periphery and tumor center were analyzed for the expression of 46 proteins, comprising three major signaling pathways as well as immune cell markers. Results were correlated to clinico-pathological variables. The differential expression of granzyme B was validated using conventional immunohistochemistry and was correlated to the cancer-specific patient survival. We found that a total of 37 proteins were differentially expressed between the tumor periphery and tumor center. Thirty-five of the proteins were upregulated in the tumor periphery compared to the center. These included proteins involved in cell proliferation, MAPK and PI3K/AKT signaling, apoptosis regulation, epithelial-to-mesenchymal transition, as well as immune cell markers. Among the most significantly upregulated proteins in the tumor periphery was granzyme B. Granzyme B upregulation in the tumor periphery correlated with a significantly reduced cancer-specific patient survival. In conclusion, this study highlights the unique cellular contexture of the tumor periphery in ccRCC. The correlation between granzyme B upregulation in the tumor periphery and patient survival suggests local selection pressure for aggressive tumor growth and disease progression. Our results underscore the potential of spatial biology for biomarker discovery in ccRCC and cancer in general.
DOI:doi:10.3390/cancers15205050
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.

kostenfrei: Volltext: https://doi.org/10.3390/cancers15205050
 kostenfrei: Volltext: https://www.mdpi.com/2072-6694/15/20/5050
 DOI: https://doi.org/10.3390/cancers15205050
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:granzyme B
 intratumoral heterogeneity
 renal cell carcinoma
 spatial biology
 tumor periphery
K10plus-PPN:1872114709
Verknüpfungen:→ Zeitschrift

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