A microRNA signature in circulating exosomes is superior to exosomal glypican-1 levels for diagnosing pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that often presents clinically at an advanced stage and that may be confused with chronic pancreatitis (CP). Conversely, CP may be misdiagnosed as PDAC leading to unwarranted pancreas resection. Therefore, early PDAC diagnosis and clear...

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Vydáno v:	Cancer letters Ročník 393; s. 86 - 93
Hlavní autoři:	Lai, Xianyin, Wang, Mu, McElyea, Samantha Deitz, Sherman, Stuart, House, Michael, Korc, Murray
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Ireland Elsevier B.V 01.05.2017 Elsevier Limited
Témata:	Acids Angiogenesis Area Under Curve Biomarkers Biomarkers, Tumor - blood Biomarkers, Tumor - genetics CA-19-9 Antigen - blood Carcinoma, Pancreatic Ductal - blood Carcinoma, Pancreatic Ductal - diagnosis Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - surgery Case-Control Studies Chromatography Chromatography, Liquid Diagnosis, Differential Exosomes Exosomes - metabolism Gene Expression Profiling - methods Glypican-1 Glypicans - blood Hematology, Oncology and Palliative Medicine Humans MicroRNAs MicroRNAs - blood MicroRNAs - genetics Oligonucleotide Array Sequence Analysis Pancreatic cancer Pancreatic Neoplasms - blood Pancreatic Neoplasms - diagnosis Pancreatic Neoplasms - genetics Pancreatic Neoplasms - surgery Pancreatitis, Chronic - blood Pancreatitis, Chronic - diagnosis Pancreatitis, Chronic - genetics Peptides Predictive Value of Tests Proteins Reproducibility of Results ROC Curve Tandem Mass Spectrometry Transcriptome United States > US sMRM RT MRM Exosomes MS/MS BSA QC ANOVA GPC1 HPLC PBS RSD HSPG IS ACN GAG CP RSP PDAC Glypican-1 MicroRNAs Pancreatic cancer LC miR ERCP Tandem mass spectrometry Internal standard Phosphate buffered saline Retention time Relative standard deviation Bovine serum albumin Endoscopic retrograde cholangiopancreatography Multiple reaction monitoring Chronic pancreatitis Pancreatic ductal adenocarcinoma Liquid chromatography Pancreatic Cancer Resistive pulse sensing Scheduled multiple reaction monitoring MicroRNA Acetonitrile Quality control Heparan sulfate proteoglycans Glycosaminoglycan Analysis of variance High performance liquid chromatography
ISSN:	0304-3835, 1872-7980, 1872-7980
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Shrnutí:	Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that often presents clinically at an advanced stage and that may be confused with chronic pancreatitis (CP). Conversely, CP may be misdiagnosed as PDAC leading to unwarranted pancreas resection. Therefore, early PDAC diagnosis and clear differentiation between PDAC and CP are crucial for improved care. Exosomes are circulating microvesicles whose components can serve as cancer biomarkers. We compared exosomal glypican-1 (GPC1) and microRNA levels in normal control subjects and in patients with PDAC and CP. We report that exosomal GPC1 is not diagnostic for PDAC, whereas high exosomal levels of microRNA-10b, (miR-10b), miR-21, miR-30c, and miR-181a and low miR-let7a readily differentiate PDAC from normal control and CP samples. By contrast with GPC1, elevated exosomal miR levels decreased to normal values within 24 h following PDAC resection. All 29 PDAC cases exhibited significantly elevated exosomal miR-10b and miR-30c levels, whereas 8 cases had normal or slightly increased CA 19-9 levels. Thus, our exosomal miR signature is superior to exosomal GPC1 or plasma CA 19-9 levels in establishing a diagnosis of PDAC and differentiating between PDAC and CP. •Liquid chromatography-tandem mass spectrometry can quantitate glypican-1 levels.•Glypican-1 levels in exosomes are not diagnostic for pancreatic cancer.•A microRNA signature in exosomes is diagnostic for pancreatic cancer.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23
ISSN:	0304-3835 1872-7980 1872-7980
DOI:	10.1016/j.canlet.2017.02.019