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Open AccessArticle

Immune-Related Circulating miR-125b-5p and miR-99a-5p Reveal a High Recurrence Risk Group of Pancreatic Cancer Patients after Tumor Resection

1
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA
2
Department of Surgery, Erasmus MC, University Medical Center Rotterdam, 3015GD Rotterdam, The Netherlands
3
Department of Pathology, Erasmus MC, University Medical Center Rotterdam, 3015GD Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Appl. Sci. 2019, 9(22), 4784; https://doi.org/10.3390/app9224784
Received: 2 October 2019 / Revised: 31 October 2019 / Accepted: 5 November 2019 / Published: 8 November 2019
(This article belongs to the Special Issue Circulating Biomarkers)
Clinical follow-up aided by changes in the expression of circulating microRNAs (miRs) may improve prognostication of pancreatic ductal adenocarcinoma (PDAC) patients. Changes in 179 circulating miRs due to cancer progression in the transgenic KrasG12D/+; Trp53R172H/+; P48-Cre (KPC) animal model of PDAC were analyzed for serum miRs that are altered in metastatic disease. In addition, expression levels of 250 miRs were profiled before and after pancreaticoduodenectomy in the serum of two patients with resectable PDAC with different progression free survival (PFS) and analyzed for changes indicative of PDAC recurrence after resection. Three miRs that were upregulated ≥3-fold in progressive PDAC in both mice and patients were selected for validation in 26 additional PDAC patients before and after resection. We found that high serum miR-125b-5p and miR-99a-5p levels after resection are significantly associated with shorter PFS (HR 1.34 and HR 1.73 respectively). In situ hybridization for miR detection in the paired resected human PDAC tissues showed that miR-125b-5p and miR-99a-5p are highly expressed in inflammatory cells in the tumor stroma, located in clusters of CD79A expressing cells of the B-lymphocyte lineage. In conclusion, we found that circulating miR-125b-5p and miR-99a-5p are potential immune-cell related prognostic biomarkers in PDAC patients after surgery. View Full-Text
Keywords: pancreatic cancer; resection; circulating microRNAs; biomarkers; progression free survival; immune cells pancreatic cancer; resection; circulating microRNAs; biomarkers; progression free survival; immune cells
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Vietsch, E.E.; Peran, I.; Suker, M.; van den Bosch, T.P.P.; van der Sijde, F.; Kros, J.M.; van Eijck, C.H.J.; Wellstein, A. Immune-Related Circulating miR-125b-5p and miR-99a-5p Reveal a High Recurrence Risk Group of Pancreatic Cancer Patients after Tumor Resection. Appl. Sci. 2019, 9, 4784.

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