Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor entity, characterized by rapid disease progression, early metastatic dissemination, and late diagnosis at advanced tumor stages. Recently, we explored the clinical impact of several microRNAs (miR) associated with proliferation, epi...
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| Format: | Article |
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MDPI AG
2020-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/1/197 |
| _version_ | 1797765651900661760 |
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| author | Moritz Reese Isabelle Flammang Zixuan Yang Sameer A. Dhayat |
| author_facet | Moritz Reese Isabelle Flammang Zixuan Yang Sameer A. Dhayat |
| author_sort | Moritz Reese |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor entity, characterized by rapid disease progression, early metastatic dissemination, and late diagnosis at advanced tumor stages. Recently, we explored the clinical impact of several microRNAs (miR) associated with proliferation, epithelial-to-mesenchymal transition (EMT), and chemoresistance in tissue and blood serum specimens of PDAC patients. Here, we evaluated the potential of these miRs as diagnostic and prognostic biomarkers in PDAC in serum exosomes and their respective EpCAM-positive (epithelial cell adhesion molecule) subset. Expression analysis by RT-qRT-PCR (real-time quantitative reverse transcription polymerase chain reaction) revealed an overexpression of miR-200b and miR-200c in serum exosomes of PDAC patients as compared to healthy controls (<i>p</i> < 0.001; <i>p</i> = 0.024) and patients with chronic pancreatitis (<i>p</i> = 0.005; <i>p</i> = 0.19). Receiver operating characteristic (ROC) curve analysis showed that a biomarker panel consisting of miR-200b and miR-200c from total and EpCAM-positive serum exosomes enhanced the diagnostic accuracy of carbohydrate antigen 19-9 (CA.19-9) to 97% (<i>p</i> < 0.0001). Univariate survival analysis revealed a correlation between shorter overall survival (OS) and high expression of miR-200c in total serum exosomes (<i>p</i> = 0.038) and miR-200b in EpCAM-positive serum exosomes (<i>p</i> = 0.032), whereas EpCAM exosomal miR-200b was also indicative of shorter OS in the subgroup of patients treated with curative intent (<i>p</i> = 0.013). Multivariate survival analysis showed that miR-200b derived from EpCAM-positive serum exosomes might serve as an independent prognostic factor in PDAC (<i>p</i> = 0.044). Our findings indicate a potential role of exosomal miR-200 as diagnostic and prognostic liquid biopsy marker in PDAC and call for validation in a larger, multicenter setting. |
| first_indexed | 2024-03-12T20:14:10Z |
| format | Article |
| id | doaj.art-ff11c08a2ee04102a1ffc34cd7aca7a0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T20:14:10Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ff11c08a2ee04102a1ffc34cd7aca7a02023-08-02T01:29:57ZengMDPI AGCancers2072-66942020-01-0112119710.3390/cancers12010197cancers12010197Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal AdenocarcinomaMoritz Reese0Isabelle Flammang1Zixuan Yang2Sameer A. Dhayat3Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, GermanyPancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor entity, characterized by rapid disease progression, early metastatic dissemination, and late diagnosis at advanced tumor stages. Recently, we explored the clinical impact of several microRNAs (miR) associated with proliferation, epithelial-to-mesenchymal transition (EMT), and chemoresistance in tissue and blood serum specimens of PDAC patients. Here, we evaluated the potential of these miRs as diagnostic and prognostic biomarkers in PDAC in serum exosomes and their respective EpCAM-positive (epithelial cell adhesion molecule) subset. Expression analysis by RT-qRT-PCR (real-time quantitative reverse transcription polymerase chain reaction) revealed an overexpression of miR-200b and miR-200c in serum exosomes of PDAC patients as compared to healthy controls (<i>p</i> < 0.001; <i>p</i> = 0.024) and patients with chronic pancreatitis (<i>p</i> = 0.005; <i>p</i> = 0.19). Receiver operating characteristic (ROC) curve analysis showed that a biomarker panel consisting of miR-200b and miR-200c from total and EpCAM-positive serum exosomes enhanced the diagnostic accuracy of carbohydrate antigen 19-9 (CA.19-9) to 97% (<i>p</i> < 0.0001). Univariate survival analysis revealed a correlation between shorter overall survival (OS) and high expression of miR-200c in total serum exosomes (<i>p</i> = 0.038) and miR-200b in EpCAM-positive serum exosomes (<i>p</i> = 0.032), whereas EpCAM exosomal miR-200b was also indicative of shorter OS in the subgroup of patients treated with curative intent (<i>p</i> = 0.013). Multivariate survival analysis showed that miR-200b derived from EpCAM-positive serum exosomes might serve as an independent prognostic factor in PDAC (<i>p</i> = 0.044). Our findings indicate a potential role of exosomal miR-200 as diagnostic and prognostic liquid biopsy marker in PDAC and call for validation in a larger, multicenter setting.https://www.mdpi.com/2072-6694/12/1/197pancreatic ductal adenocarcinomamicrornaliquid biopsyexosomesepithelial cell adhesion molecule |
| spellingShingle | Moritz Reese Isabelle Flammang Zixuan Yang Sameer A. Dhayat Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal Adenocarcinoma Cancers pancreatic ductal adenocarcinoma microrna liquid biopsy exosomes epithelial cell adhesion molecule |
| title | Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal Adenocarcinoma |
| title_full | Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal Adenocarcinoma |
| title_fullStr | Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal Adenocarcinoma |
| title_short | Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal Adenocarcinoma |
| title_sort | potential of exosomal microrna 200b as liquid biopsy marker in pancreatic ductal adenocarcinoma |
| topic | pancreatic ductal adenocarcinoma microrna liquid biopsy exosomes epithelial cell adhesion molecule |
| url | https://www.mdpi.com/2072-6694/12/1/197 |
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