Abstract
Pancreatic ductal adenocarcinoma (PDAC) is difficult to distinguish from autoimmune pancreatitis (AIP) because of their clinical and radiological similarities, and therefore simple and minimally invasive surrogate markers for differential diagnosis would be useful. In our previous studies, we identified four microRNAs (miRNAs)–miR-7, miR-34a, miR-181d, and miR-193b –as MAPK-associated microRNAs whose expression was altered significantly with upregulation of the MAPK signaling pathway. Recently it has been reported that these miRNAs could be used as biomarkers in serum samples for accurate diagnosis of pancreatic lesions. The aim of the present study was to evaluate whether these MAPK-associated miRNAs in serum could be used as biomarkers for differentiating PDAC from AIP. We enrolled 69 patients with PDAC, 26 with intraductal papillary mucinous neoplasm (IPMN) and 15 with AIP. The expression of MAPK-associated miRNAs in serum was measured by quantitative real-time PCR. The 2-ΔCT method was used to quantify the expression of miRNAs, and the data were normalized using spiked-in synthetic cel-miR-39. Patients with PDAC or IPMN showed significantly higher amounts of serum MAPK-associated miRNAs than those with AIP (p<0.009 for miR-7, p<0.002 for miR-34a, p<0.001 for miR-181d, p<0.002 for miR-193b). ROC curve analysis demonstrated that these miRNAs had an area under the ROC curve (AUC) of 0.723–0.882 for differentiation between PDAC or IPMN from AIP. Furthermore, serum miR-181d was significantly associated with the presence of metastasis in patients with PDA (p = 0.014). Serum MAPK-associated miRNAs could be novel noninvasive biomarkers for differentiation between PDAC or IPMN and AIP.
Highlights
Pancreatic cancer is one of the major causes of cancer death worldwide [1, 2]
We identified four miRNAs–miR-7, miR-34a, miR-181d and miR193b –that are associated with constitutive activation of mitogen-activated protein kinase (MAPK) in pancreatic cancer cells [14]
Pancreatic ductal adenocarcinoma (PDAC) is a malignant disease with a poor prognosis, whereas Autoimmune pancreatitis (AIP) is a benign inflammatory disease that mimics PDAC both clinically and radiologically
Summary
Pancreatic cancer is one of the major causes of cancer death worldwide [1, 2]. Despite advances in diagnostic and therapeutic techniques, the 5-year survival rate of patients with pancreatic cancer remains less than 10% [3]. Autoimmune pancreatitis (AIP) is a rare form of chronic. Pancreatic cancer is sometimes difficult to distinguish from AIP because of their clinical and radiological similarities [4], and accurate diagnosis is essential. The development of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has made it possible to obtain samples of pancreatic tissue in diagnostic procedures, the technique has certain limitations, such as invasiveness and difficulty in obtaining a sufficient number of cells, and more effective and minimally invasive diagnostic measures would be useful
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