Discrimination between Adenocarcinoma and Normal Pancreatic Ductal Fluid by Proteomic and Glycomic Analysis

Porterfield, Mindy; Zhao, Peng; Han, Haiyong; Cunningham, J. T.; Aoki, Kazuhiro; Hoff, Daniel D. Von; Demeure, Michael J.; Pierce, J. Michael; Tiemeyer, Michael; Wells, Lance

doi:10.1021/pr400422g

Cited by 35 publications

(35 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, several microarray analyses have isolated Reg family genes as novel molecules overexpressed in inflammatory bowel disease (3,11), colorectal cancers (27), the gastritisgastric cancer sequence (7,20), and pancreatic cancers (15), and, therefore, much attention has been focused on the roles of REG family proteins in the GI tract. In the present study, to clarify why similar family proteins are concomitantly produced in the GI mucosa, we first investigated the expression profiles of Reg family genes throughout the GI tract.…”

Section: Discussionmentioning

confidence: 99%

Expression ofRegfamily genes in the gastrointestinal tract of mice treated with indomethacin

Sun

Fukui

Hara

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Regenerating gene (Reg) family proteins, which are classified into four types, commonly act as trophic and/or antiapoptotic factors in gastrointestinal (GI) diseases. However, it remains unclear how these proteins coordinate their similar roles under such pathophysiological conditions. Here, we investigated the interrelationships of Reg family gene expression with mucosal cell proliferation and apoptosis in nonsteroidal anti-inflammatory drug (NSAID)-induced GI injury. GI injury was induced by subcutaneous injection of indomethacin into Reg I knockout (KO) and wild-type (WT) mice, and its severity was scored histopathologically. Temporal changes in the expression of Reg family genes, mucosal proliferation, and apoptosis were evaluated throughout the GI tract by real-time RT-PCR, Ki-67 immunoreactivity, and TUNEL assay, respectively. Reg I, Reg III family, and Reg IV were predominantly expressed in the upper, middle, and lower GI mucosa, respectively. Expression of Reg I and Reg III family genes was upregulated in specific portions of the GI tract after indomethacin treatment. Ki-67-positive epithelial cells were significantly decreased in the gastric and small-intestinal mucosa of Reg I KO mice under normal conditions. After treatment with indomethacin, the number of TUNEL-positive cells was significantly greater throughout the GI mucosa in Reg I KO mice than in WT mice. Expression of Reg I was independent of that of other Reg family genes in, not only normal GI tissues, but also indomethacin-induced GI lesions. Members of the Reg gene family show distinct profiles of expression in the GI tract, and Reg I independently plays a role in protecting the GI mucosa against NSAID-induced injury.Reg; nonsteroidal anti-inflammatory drug; proliferation; apoptosis; gastrointestinal mucosa NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) are commonly prescribed worldwide for patients with arthritis or cardiac and cerebrovascular diseases (16). Upper gastrointestinal (GI) damage is a major adverse effect of NSAID use (16), and, moreover, recent evidence suggests that NSAIDs are responsible for mucosal injury, not only in the upper, but also the lower GI tract (10, 16). Prostaglandin synthesis is considered to play a pivotal role in the mechanism of NSAID-induced GI damage (21); however, its pathophysiology still remains to be elucidated.The regenerating gene (Reg) was originally isolated from rat regenerating pancreatic islet cells, and its human homolog was named REG I␣ (23). Recently, many Reg-related genes have been isolated and shown to constitute a multigene family (types I-IV) (8). We have previously reported that REG I␣ and REG IV are involved in the pathophysiology of GI inflammation (5, 17) and that, moreover, they act as trophic and/or antiapoptotic factors under inflammatory conditions (17, 18). Other investigators have reported that Reg III family genes are overexpressed in inflamed GI mucosa (11,13) and that their products, including REG I␣ and REG IV proteins, may exert trophic and/or antiapoptotic effects on panc...

show abstract

Section: Discussionmentioning

confidence: 99%

Expression ofRegfamily genes in the gastrointestinal tract of mice treated with indomethacin

Sun

Fukui

Hara

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Reg4, the most recently discovered member of the family, was reported to be elevated in PDAC and proposed to be a diagnostic marker [14, 15]. Moreover, a proteomic analysis of pancreatic juice demonstrated increased levels of Reg1A, Reg1B and Reg3A proteins in PDAC, in comparison to normal subjects and patients with pancreatitis [16]. However, the involvement of Reg proteins in the onset and progression of PDAC has yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Reg proteins promote acinar-to-ductal metaplasia and act as novel diagnostic and prognostic markers in pancreatic ductal adenocarcinoma

Wang

Zogopoulos

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to inflammation and/or injuries. The aim of this study was to establish a role for Reg proteins in the development of PDAC and their clinical value as biomarkers. We found that Reg1A and Reg3A/G were highly expressed in the ADM tissues by immunohistochemistry. In the 3-dimensional culture of mouse acinar cells, Reg3A promoted ADM formation with concurrent activation of mitogen-acitvated protein kinase. Upregulation of Reg1A and Reg1B levels was observed as benign ductal epithelium progresses from PanIN to invasive PDAC. Patients with PDAC showed significantly higher serum levels of Reg1A and Reg1B than matching healthy subjects. These results were further validated by the quantification of Reg 1A and 1B mRNA levels in the microdissected tissues (22- and 6-fold increases vs. non-tumor tissues). Interestingly, patients with higher levels of Reg1A and 1B exhibited improved survival rate than those with lower levels. Furthermore, tissue expressions of Reg1A, Reg1B, and Reg4 could differentiate metastatic PDAC in the liver from intrahepatic cholangiocarcinoma with 92% sensitivity and 95% specificity. Overall, our results demonstrate the upregulation of Reg proteins during PDAC development. If validated in larger scale, Reg1A and Reg1B could become clinical markers for detecting early stages of PDAC, monitoring therapeutic response, and/or predicting patient's prognosis.

show abstract

“…In contrast, elevated GP2 levels were found in pancreatic ductal fluid of pancreatic cancer but not of pancreatitis patients recently [41].…”

Section: Discussionmentioning

confidence: 77%

Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2

Roggenbuck

Goihl

Hanack

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2 DOI 10.1515/cclm-2016-0797 Received September 6, 2016 accepted October 10, 2016; previously published online November 12, 2016 Abstract Background: Glycoprotein 2 (GP2), the pancreatic major zymogen granule membrane glycoprotein, was reported to be elevated in acute pancreatitis in animal models. Methods: Enzyme-linked immunosorbent assays (ELISAs) were developed to evaluate human glycoprotein 2 isoform alpha (GP2a) and total GP2 (GP2t) as specific markers for acute pancreatitis in sera of 153 patients with acute pancreatitis, 26 with chronic pancreatitis, 125 with pancreatic neoplasms, 324 with non-pancreatic neoplasms, 109 patients with liver/biliary disease, 67 with gastrointestinal disease, and 101 healthy subjects. GP2a and GP2t levels were correlated with procalcitonin and C-reactive protein in 152 and 146 follow-up samples of acute pancreatitis patients, respectively.

show abstract

Discrimination between Adenocarcinoma and Normal Pancreatic Ductal Fluid by Proteomic and Glycomic Analysis

Cited by 35 publications

References 63 publications

Expression ofRegfamily genes in the gastrointestinal tract of mice treated with indomethacin

Expression ofRegfamily genes in the gastrointestinal tract of mice treated with indomethacin

Reg proteins promote acinar-to-ductal metaplasia and act as novel diagnostic and prognostic markers in pancreatic ductal adenocarcinoma

Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2

Contact Info

Product

Resources

About