Universität zu Köln

Knipper, Karl ORCID: 0009-0008-7133-3538, Lyu, Su Ir ORCID: 0009-0002-4125-6048, Tzitzili, Eleni ORCID: 0000-0002-2465-9585, Spielmann, Sarah-Michele, Bruns, Christiane J. ORCID: 0000-0001-6590-8181, Schmidt, Thomas ORCID: 0000-0002-7166-3675, Popp, Felix C. ORCID: 0000-0002-1690-6777 and Quaas, Alexander ORCID: 0000-0002-3537-6011 (2025). Loss of Argininosuccinate Synthetase-1 (ASS1) Occurs in Esophageal Adenocarcinoma and Represents a Promising Biomarker for Therapy with Pegargiminase. Cancers, 17 (22). MDPI. ISSN 2072-6694

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Abstract

[Artikel-Nr.: 3624] Background/Objectives: Despite the introduction of targeted therapies such as Nivolumab, survival outcomes for patients with esophageal adenocarcinoma remain poor. During tumorigenesis, some tumors develop auxotrophy by downregulation of Argininosuccinate Synthetase-1 (ASS1), making them reliant on external arginine supply and thus potentially susceptible to arginine deprivation therapy. Arginine deprivation therapy with agents such as pegargiminase has shown improved survival in patients with pleural mesothelioma exhibiting ASS1 loss in tumor cells. Therefore, we investigated the prevalence of ASS1 loss in esophageal adenocarcinoma. Methods: First, we compared the staining patterns of three antibodies for ASS1 with RNA in situ Scope analysis results to identify the most reliable antibody for ASS1 immunohistochemical staining in esophageal adenocarcinoma. Subsequently, we performed ASS1 immunohistochemical staining on samples from 97 patients who underwent curative resection. The staining results were classified into three categories based on expression levels: negative, low-positive, and positive. Results: Among all included patients, 6.2% exhibited an ASS1 loss, and 6.2% showed low ASS1 expression. Notably, patients with an ASS1 loss did not demonstrate a response to neoadjuvant therapy. Patients with ASS1 loss or low expression were significantly younger. Conclusions: Our findings indicate that approximately 12.4% of patients with esophageal adenocarcinoma may be eligible and could potentially benefit from arginine deprivation therapy. This underscores the urgent need for clinical trials evaluating the efficacy of pegargiminase in this patient population. Additionally, incorporating ASS1 immunohistochemical staining into pre-neoadjuvant biopsy assessments should be considered to optimize neoadjuvant treatment strategies and advance the implementation of personalized cancer therapy.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Knipper, Karl UNSPECIFIED https://orcid.org/0009-0008-7133-3538 UNSPECIFIED Lyu, Su Ir UNSPECIFIED https://orcid.org/0009-0002-4125-6048 UNSPECIFIED Tzitzili, Eleni UNSPECIFIED https://orcid.org/0000-0002-2465-9585 UNSPECIFIED Spielmann, Sarah-Michele UNSPECIFIED UNSPECIFIED 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
URN:	urn:nbn:de:hbz:38-800871
Identification Number:	10.3390/cancers17223624
Journal or Publication Title:	Cancers
Volume:	17
Number:	22
Number of Pages:	12
Date:	11 November 2025
Publisher:	MDPI
ISSN:	2072-6694
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 esophageal adenocarcinoma ; Argininosuccinate Synthetase 1; ASS1 ; pegargiminase ; personalized medicine ; biomarker English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80087