title: 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.
authors: Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
authors: Muxing
authors: M
authors: Kang
authors: Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
authors: Wenjie
authors: W
authors: Qin
authors: Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
authors: Miranbieke
authors: M
authors: Buya
authors: Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
authors: Xin
authors: X
authors: Dong
authors: Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
authors: Wen
authors: W
authors: Zheng
authors: Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
authors: Wenjie
authors: W
authors: Lu
authors: Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
authors: Jian
authors: J
authors: Chen
authors: Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
authors: Qingqu
authors: Q
authors: Guo
authors: Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China. Electronic address: wuyulian@medmail.com.cn.
authors: Yulian
authors: Y
authors: Wu
mesh_terms: D000230:Adenocarcinoma / Q000150:complications; D000368:Aged; D000581:Amidohydrolases / Q000032:analysis / Q000502:physiology*; D000818:Animals; D015415:Biomarkers; D021441:Carcinoma, Pancreatic Ductal / Q000150:complications; D045744:Cell Line, Tumor; D003543:Cysteamine / Q000097:blood; D003920:Diabetes Mellitus / Q000175:diagnosis*; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis / Q000502:physiology; D005978:Glutathione / Q000097:blood; D006801:Humans; D007515:Islets of Langerhans / Q000503:physiopathology*; D051379:Mice; D008875:Middle Aged; D018384:Oxidative Stress; D047495:PPAR gamma / Q000097:blood; D010190:Pancreatic Neoplasms / Q000150:complications*; D010257:Paraneoplastic Syndromes / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D058851:GPI-Linked Proteins; D047495:PPAR gamma; D003543:Cysteamine; D000581:Amidohydrolases; C022314:pantetheinase; D005978:Glutathione
keywords: Early screening; Oxidative stress; Pancreatic cancer associated new-onset diabetes; Paraneoplastic diabetes; VNN1