VNN1, a potential biomarker for pancreatic cancer-associated new-onset diabetes, aggravates paraneoplastic islet dysfunction by increasing oxidative stress
Abstract
In our previous clinical microarray analysis, we were the first to report on Vanin-1 (VNN1) as a novel clinically derived biomarker of pancreatic cancer-associated new-onset diabetes (PCAND). The functional mechanisms of VNN1 in the pathogenesis of PCAND, however, are not completely understood. In the present study, we further extend our previous clinical study to include laboratory research. The functions and mechanisms of neoplastic overexpressed VNN1 in PCAND have been explored using a co-culture model. Furthermore, the serum concentrations and discrimination power of downstream molecules of VNN1 were tested in a PCAND cohort. Pancreatic ductal adenocarcinoma (PDA) overexpressed VNN1 further aggravates paraneoplastic islet dysfunction; decreases in GSH/PPAR-γ concentrations and increases in ROS/cysteamine might be primary cause of this effect. Clinical serum analyses revealed that the expression profiles of these molecules were aberrant in the PCAND group. Our results further demonstrated that PCAND is a type of paraneoplastic diabetes. As the only clinically derived biomarker for PCAND screening available today, the biological role of VNN1 in triggering oxidative stress within the pancreatic microenvironment is important. The molecules downstream of VNN1 are also potential biomarkers for PCAND screening.
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Early detection of pancreatic cancer
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- Authors
- Kang, M., Qin, W., Buya, M., Dong, X., Zheng, W., Lu, W., Chen, J., Guo, Q., & Wu, Y.
- Affiliations
- Second Affiliated Hospital of Zhejiang University (CN)
- Corresponding author
- Wu, Yulian
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 373
- Issue
- 2
- Pages
- 241-250
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2253972966
- Cited by
- 63
- References
- 40
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 10 · 2023: 14 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 1
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81172158, 81272332, 81301889, 81001094, 81372620)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Keywords
- vanin-1, pancreatic ductal adenocarcinoma, oxidative stress, pancreatic islet dysfunction, glutathione, PPARγ, reactive oxygen species, cysteamine, biomarkers, serum biomarkers
- MeSH terms
- Adenocarcinoma, Aged, Amidohydrolases, Animals, Cysteamine, Diabetes Mellitus, Female, Glutathione, Humans, Islets of Langerhans, Middle Aged, Pancreatic Neoplasms, Paraneoplastic Syndromes, Biomarkers, Oxidative Stress, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, PPAR gamma, Mice, GPI-Linked Proteins
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