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

Abstract

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 micro-vesicles 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.

Multiple antibodies identify glypican-1 associated with exosomes from pancreatic cancer cells and serum from patients with pancreatic cancer

“…As such, exosomes from the serum of patients emerged as an attractive approach to possibly detect cancerous lesions and monitor and predict outcome of cancer patients. Several studies have reproduced our original findings related to enrichment of GPC1 in cancer exosomes, including in breast cancer exosomes, colorectal, esophageal and pancreas cancer [2][3][4][5]8,[18][19][20] (Table 1). Additionally, most of these reports show that such enrichment of GPC1 in exosomes can serve as biomarker.…”

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

“…Sohn W's studies revealed that the levels of circulating exosomal miR-181, miR-221, and miR-224 were significant higher in HCC patients than in chronic hepatitis B patients; however, there were little differences in the level of circulating miRNAs between these two groups [67]. The level of circulating exosomal miR-10b and miR-30c was significantly elevated in 29 PDAC patients relative to chronic pancreatitis patients; however, the level of CA 19-9 was normal or slightly increased in 8 cases [68]. Goto T's study showed that circulating exosomal miR-191, miR-21, and miR451a levels were superior to circulating miRNA levels for differentiating PDAC patients from intraductal papillary mucinous neoplasm (IPMN) patients [69].…”

The Dual Regulatory Role of MiR-181a in Breast Cancer

“…Thus far, ex-miR-181a has been identified in exosomes derived from breast cancer cells [63], dendritic cells [64], T cells (T cell line J77) [64], stem cells [65, 66], and esophageal cancer cells [67]. It was also found in serum exosomes of patients with ovarian cancer, pancreatic ductal adenocarcinoma, and thyroid cancer [68-70]. ex-miR-181a was found to be one of the twenty most abundant human plasma exosomal miRNAs [71].…”