Universität zu Köln

Knipper, Karl ORCID: 0009-0008-7133-3538, Hussein, Yussra, Simon, Adrian Georg ORCID: 0000-0002-2709-863X, Fretter, Caroline, Damanakis, Alexander I. ORCID: 0000-0002-1155-5541, Zhao, Yue ORCID: 0000-0002-6790-3402, Bruns, Christiane J. ORCID: 0000-0001-6590-8181, Schmidt, Thomas ORCID: 0000-0002-7166-3675, Popp, Felix C. ORCID: 0000-0002-1690-6777, Quaas, Alexander ORCID: 0000-0002-3537-6011, Lyu, Su Ir ORCID: 0009-0002-4125-6048, Heise, Michael, Marusch, Frank, Siech, Marco, Mosa, Tawfik, Schniewind, Bodo, Tepel, Jürgen, Hartwig, Werner, Prinz, Christoph, Rau, Bettina M., Niedergethmann, Marco, Kube, Rainer, Saada, George, Hiller, Wolfgang and Settmacher, Utz (2024). Upregulation of the histone γ-H2AX correlates with worse patient survival and basal-like subtype in pancreatic ductal adenocarcinoma. Journal of Cancer Research and Clinical Oncology, 150 (3). pp. 1-8. Springer Nature. ISSN 1432-1335

PDF s00432-024-05681-x.pdf Bereitstellung unter der CC-Lizenz: Creative Commons Attribution. Download (4MB)

Abstract

[Artikel-Nr.: 137] Purpose: Patients with pancreatic ductal adenocarcinoma (PDAC) have yet to experience significant benefits from targeted therapy. Olaparib is currently the only active substance in BRCA-mutated PDACs that successfully influences the DNA repair of carcinoma cells. H2AX belongs to the histone family and is known as a part of the DNA repair system. The inhibition of γ-H2AX could lead to the inhibition of mitotically active tumor cells. Therefore, we aimed to evaluate the predictive value of the γ-H2AX in patients with PDAC. Methods: All included patients ( n = 311) received a pancreatic resection with curative intention in one of our PANCALYZE study centers. Subsequently, they were enrolled in a standardized follow-up protocol. Immunohistochemical stainings for γ-H2AX were conducted on tissue microarrays. Results: Patients exhibiting high levels of γ-H2AX expression experience more frequent R1 resections, indicating advanced tumor stages in this subgroup. Additionally, patients with high γ-H2AX expression demonstrated significantly poorer survival compared to those with low expression (median OS: 15 vs. 25 months, p < 0.001). In multivariate analyses, high γ-H2AX expression could be identified as an independent risk factor for worse patient survival. Moreover, high γ-H2AX expression could be more frequently observed in the more aggressive basal-like subtype. Conclusion: γ-H2AX can be characterized as a predictive biomarker for poorer patient survival. Consequently, upcoming clinical trials focused on the efficacy of targeted therapies influencing the DNA repair system and radiotherapy should evaluate γ-H2AX as a potential biomarker for therapy response. Furthermore, γ-H2AX may serve as a viable target for treatment in the future.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Knipper, Karl UNSPECIFIED https://orcid.org/0009-0008-7133-3538 UNSPECIFIED Hussein, Yussra UNSPECIFIED UNSPECIFIED UNSPECIFIED Simon, Adrian Georg UNSPECIFIED https://orcid.org/0000-0002-2709-863X UNSPECIFIED Fretter, Caroline UNSPECIFIED UNSPECIFIED UNSPECIFIED Damanakis, Alexander I. UNSPECIFIED https://orcid.org/0000-0002-1155-5541 UNSPECIFIED Zhao, Yue UNSPECIFIED https://orcid.org/0000-0002-6790-3402 UNSPECIFIED Bruns, Christiane J. UNSPECIFIED https://orcid.org/0000-0001-6590-8181 UNSPECIFIED Schmidt, Thomas UNSPECIFIED https://orcid.org/0000-0002-7166-3675 UNSPECIFIED Popp, Felix C. UNSPECIFIED https://orcid.org/0000-0002-1690-6777 UNSPECIFIED Quaas, Alexander UNSPECIFIED https://orcid.org/0000-0002-3537-6011 UNSPECIFIED Lyu, Su Ir UNSPECIFIED https://orcid.org/0009-0002-4125-6048 UNSPECIFIED Heise, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Marusch, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Siech, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Mosa, Tawfik UNSPECIFIED UNSPECIFIED UNSPECIFIED Schniewind, Bodo UNSPECIFIED UNSPECIFIED UNSPECIFIED Tepel, Jürgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartwig, Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Prinz, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Rau, Bettina M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niedergethmann, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Kube, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Saada, George UNSPECIFIED UNSPECIFIED UNSPECIFIED Hiller, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Settmacher, Utz UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-815287
Identification Number:	10.1007/s00432-024-05681-x
Journal or Publication Title:	Journal of Cancer Research and Clinical Oncology
Volume:	150
Number:	3
Page Range:	pp. 1-8
Number of Pages:	8
Date:	19 March 2024
Publisher:	Springer Nature
ISSN:	1432-1335
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Chirurgie > Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Transplantationschirurgie Faculty of Medicine > Pathologie und Neuropathologie > Institut für Pathologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Pancreatic ductal adenocarcinoma ; H2AX ; Histone ; DNA repair ; Biomarker English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81528