title: Annexin A10 is a candidate marker associated with the progression of pancreatic precursor lesions to adenocarcinoma.
abstract: Annexins are a multigene family of calcium and phospholipid-binding proteins that play important roles in calcium signaling, cell motility, differentiation and proliferation. Our previous mass spectrometry-based proteomics study revealed that annexin A10 (ANXA10) was uniquely overexpressed in pancreatic CD24+ adenocarcinoma cells that were dissected from clinical PDAC tissues but was absent in CD24- adjacent normal cells. The correlation between ANXA10 expression and the progression of pancreatic cancer remains unknown. In this study, we performed an immunostaining assay to evaluate ANXA10 expression in 155 primary human tissue specimens, including normal pancreas, chronic pancreatitis (CP), pancreatic adenocarcinoma (PDAC), pancreatic intraepithelial neoplasia (PanIN, the most important precursor of PDAC), and intraductal papillary mucinous neoplasm (IPMN). The immunostaining result showed that ANXA10 was significantly overexpressed in PanINs, IPMNs, and PDACs but negative in normal pancreas and the majority of chronic pancreatitis tissues. Statistical analysis revealed that ANXA10 expression was significantly associated with PDAC and its precursor lesions (p<0.0001). Abundant ANXA10 expression was predominantly present in pancreatic ductal epithelial cells of PanINs, IPMNs, and tumor cells of PDACs. Since PDAC develops through a series of PanINs which in turn arise from pancreatic ducts, the consistent overexpression of ANXA10 in ductal epithelial cells in PanINs and PDACs but negative in normal pancreatic ducts suggests that ANXA10 could serve as a potential marker indicating the presence of PDAC at its earliest precancerous stages. Double immunostaining of ANXA10 and CD24 showed that there was a large overlap between these two markers in PDAC and high-grade neoplasia lesions. The statistical analysis showed that the coexpression of ANXA10 and CD24 was significantly correlated with the progression of pancreatic precursor lesions towards PDACs.
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, United States of America.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, United States of America.|Department of Toxicology, School of Public Health, Shenyang Medical College, Liaoning, China.
authors.forename: Xiucong
authors.initials: X
authors.lastname: Pei
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, United States of America.
authors.forename: Zhijing
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, United States of America.
authors.forename: David M
authors.identifier: http://orcid.org/0000-0001-7731-0232
authors.initials: DM
authors.lastname: Lubman
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics / Q000473:pathology*; D017302:Annexins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D051927:CD24 Antigen / Q000097:blood / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D010179:Pancreas / Q000378:metabolism; D010183:Pancreatic Ducts / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000097:blood / Q000235:genetics / Q000473:pathology*
chemical_list: C121387:ANXA10 protein, human; D017302:Annexins; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human