Exosome‐encapsulated microRNA‐4525, microRNA‐451a and microRNA‐21 in portal vein blood is a high‐sensitive liquid biomarker for the selection of high‐risk pancreatic ductal adenocarcinoma patients

Abstract

Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with poor prognosis. This is due to late diagnosis and lack of reliable prognostic biomarkers. In this study, we focused on exosomal microRNA (miRNA) in portal vein blood (PVB) as a potential biomarker to identify patients at high‐risk for recurrence and poor postoperative outcome. Methods Exosomal miR‐4525, miR‐451a and miR‐21 expressions were assessed using PVB and peripheral blood (PB) collected from 55 PDAC patients during curative pancreatectomy. Correlation between the miRNA expressions and clinical outcomes, and target genes expressions was investigated. Results Exosomal miR‐4525, miR‐451a and miR‐21 levels were upregulated in PVB, which were higher than those in the PB. High expression of miR‐4525, miR‐451a and miR‐21 in PVB was associated with recurrence with a higher sensitivity, specificity, and accuracy than that in PB. Cox regression analysis showed miR‐4525, miR‐451a and miR‐21 levels in PVB were independent prognostic factors for overall survival and disease‐free survival. There was a negative correlation between the expressions of miR‐4525 and MEN1 mRNA, miR‐451a and CAB39 mRNA, and t miR‐21 and PDCD4 mRNA. Conclusions miR‐4525, miR‐451a and miR‐21 in PVB are potential biomarkers identifying patients at high‐risk for recurrence and poor survival in resected PDAC patients.

The involvement of exosomes in the diagnosis and treatment of pancreatic cancer

“…Furthermore, it has also been reported that miRNA-16a and miRNA-196a, together with CA19-9 [60], provided a positive outcome towards the identification of stage I of PC [61], suggesting that these exosomal microRNAs can also be used as PC peripheral biomarkers [62]. Also, in Kawamura's study, miR-4525, miR-451a, and miR-21 derived from portal vein have been proved possible biomarkers to determine the likelihood of recurrence and poor survival in patients with pancreatic cancer [63]. Furthermore, CKAP4, a DKK1 receptor, and secreted by exosomes, was also found to be a potential biomarker for pancreatic cancer [64].…”

“…miR-4525, miR-451a, and miR-21 Diagnosis [63] The plasma of patients with primary pancreatic ductal adenocarcinoma and plasma from healthy controls.…”

The Role of Exosomes in Pancreatic Cancer From Bench to Clinical Application: An Updated Review

“…Goto et al (50) reported that exosomal miR-21 isolated from pancreatic juice using ultracentrifugation could also differentiate PDAC and chronic pancreatitis (CP). The patients with PDAC had a higher level of exosomal miR-451 than the HP, and the expression level of miR-451 wassignificantly correlated with recurrence and survival time (48,51). Plasma exosomal miR-196a and miR-1246 also showed diagnostic value for localized pancreatic cancer (52).…”

“…Many studies have highlighted the possibility of clinical translation of exosomal biomarkers in PDAC ( Table 2). Plasma exosomal miR-21 could be used to differentiate patients with PDAC, intraductal papillary mucinous neoplasm (IPMN) and healthy participants (HP) (48,49). Goto et al (50) reported that exosomal miR-21 isolated from pancreatic juice using ultracentrifugation could also differentiate PDAC and chronic pancreatitis (CP).…”

Accurate Cancer Diagnosis and Stage Monitoring Enabled by Comprehensive Profiling of Different Types of Exosomal Biomarkers: Surface Proteins and miRNAs

“…Previous studies indicate that miRNA-451a, miRNA-21, and miRNA-10b are highly expressed in pancreatic cancer cells and pancreatic cancer tissues. [12,36,37] Therefore, MB-451a, MB-21, and MB-10b were designed to probe these miRNAs (Table S2, Supporting Information). The ability of MBs to detect miRNAs was first evaluated in homogeneous solution.…”