ArticlePloS one2017
Reduced expression of argininosuccinate synthetase 1 has a negative prognostic impact in patients with pancreatic ductal adenocarcinoma.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- SSRP1/SLC3A2 Axis in Arginine Transport: A New Target for Overcoming Immune Evasion and Tumor Progression in Peripheral T-Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PEGylated RecombinantACS biomaterials science & engineering · 2024Article
- Development of a Two-Dimensional Liquid Chromatographic Method for Analysis of Urea Cycle Amino Acids.Molecules (Basel, Switzerland) · 2024Article
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- GCN2 inhibition sensitizes arginine-deprived hepatocellular carcinoma cells to senolytic treatment.Cell metabolism · 2022Article
- Activation of VIPR1 suppresses hepatocellular carcinoma progression by regulating arginine and pyrimidine metabolism.International journal of biological sciences · 2022Article
- Cisplatin Resistance and Redox-Metabolic Vulnerability: A Second Alteration.International journal of molecular sciences · 2021Review
- Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation.Cell reports · 2021Article
- High-performance Collective Biomarker from Liquid Biopsy for Diagnosis of Pancreatic Cancer Based on Mass Spectrometry and Machine Learning.Journal of Cancer · 2021Article
- Genomic Copy Number Variants in CML Patients With the Philadelphia Chromosome (Ph+): An Update.Frontiers in genetics · 2021Article
- [HuArgI (co)-PEG5000]-induced arginine deprivation leads to autophagy dependent cell death in pancreatic cancer cells.Investigational new drugs · 2020Article
- Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors.Nature cancer · 2020Article
- Histone deacetylase inhibition is synthetically lethal with arginine deprivation in pancreatic cancers with low argininosuccinate synthetase 1 expression.Theranostics · 2020Article
- Exploiting Arginine Auxotrophy with Pegylated Arginine Deiminase (ADI-PEG20) to Sensitize Pancreatic Cancer to Radiotherapy via Metabolic Dysregulation.Molecular cancer therapeutics · 2019Article
- Novel miR-29b target regulation patterns are revealed in two different cell lines.Scientific reports · 2019Article
- Imaging of glucose metabolism by 13C-MRI distinguishes pancreatic cancer subtypes in mice.eLife · 2019Article
- Rewiring urea cycle metabolism in cancer to support anabolism.Nature reviews. Cancer · 2018Review
- Arginine and the metabolic regulation of nitric oxide synthesis in cancer.Disease models & mechanisms · 2018Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme for arginine biosynthesis, is expressed in many types of human malignancies. Recent studies showed that ASS1 may have tumor suppressor function and that ASS1 deficiency is associated with clinical aggressiveness in nasopharyngeal carcinoma, myxofibrosarcomas and bladder cancer. The goal of this study was to evaluate the prognostic impact of ASS1 expression in patients with pancreatic ductal adenocarcinoma (PDAC). Our study included two independent cohorts: untreated cohort, which was comprised of 135 patients with PDAC who underwent pancreatoduodenectomy (PD) without pre-operative neoadjuvant therapy, and treated cohort, which was comprised of 122 patients with PDAC who have completed neoadjuvant therapy and PD. The expression level of ASS1 was evaluated by immunohistochemistry and the results were correlated with clinicopathologic parameters and survival using SPSS statistics. Our study showed that 12% of PDAC in untreated cohort and 15% of PDAC in treated cohort has low expression of ASS1 (ASS1-low). ASS1-low was associated with higher recurrence (p = 0.045), shorter disease-free survival (DFS, 4.8 ± 1.6 months vs 15.3 ± 2.2 months, p = 0.001) and shorter overall survival (OS, 14.6 ± 6.4 months vs 26.5 ± 3.5 months, p = 0.005) in untreated cohort and shorter OS in treated cohort compared to ASS1-high tumors. In multivariate analysis, ASS1-low (HR: 0.45, 95% CI: 0.26-0.79, p = 0.005) was an independent prognostic factor for DFS in untreated cohort and an independent prognostic factor for OS (HR: 0.56, 95% CI: 0.32-0.97, p = 0.04) in treated cohort. Our results provide supporting evidence for future clinical trial using arginine deprivation agents either alone or in combination with conventional chemotherapy in treating pancreatic cancer.
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