Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma Patients
Background: In pancreatic ductal adenocarcinoma (PDAC), the characterization of circulating tumor cells (CTCs) opens new insights into cancer metastasis as the leading cause of cancer-related death. Here, we focused on the expression of retinoic acid receptor responder 1 (RARRES1) on CTCs as a novel...
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MDPI AG
2022-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/18/4405 |
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| author | Christine Nitschke Benedikt Markmann Marie Tölle Jolanthe Kropidlowski Yassine Belloum Mara R. Goetz Hartmut Schlüter Marcel Kwiatkowski Marianne Sinn Jakob Izbicki Klaus Pantel Cenap Güngör Faik G. Uzunoglu Harriet Wikman |
| author_facet | Christine Nitschke Benedikt Markmann Marie Tölle Jolanthe Kropidlowski Yassine Belloum Mara R. Goetz Hartmut Schlüter Marcel Kwiatkowski Marianne Sinn Jakob Izbicki Klaus Pantel Cenap Güngör Faik G. Uzunoglu Harriet Wikman |
| author_sort | Christine Nitschke |
| collection | DOAJ |
| description | Background: In pancreatic ductal adenocarcinoma (PDAC), the characterization of circulating tumor cells (CTCs) opens new insights into cancer metastasis as the leading cause of cancer-related death. Here, we focused on the expression of retinoic acid receptor responder 1 (RARRES1) on CTCs as a novel marker for treatment failure and early relapse. Methods: The stable isotope labeling of amino acids in cell culture (SILAC)—approach was applied for identifying and quantifying new biomarker proteins in PDAC cell lines HPDE and its chemoresistant counterpart, L3.6pl-Res. Fifty-five baseline and 36 follow-up (FUP) peripheral blood samples were processed via a marker-independent microfluidic-based CTC detection approach using RARRES1 as an additional marker. Results: SILAC-based proteomics identified RARRES1 as an abundantly expressed protein in more aggressive chemoresistant PDAC cells. At baseline, CTCs were detected in 25.5% of all PDAC patients, while FUP analysis (median: 11 months FUP) showed CTC detection in 45.5% of the resected patients. CTC positivity (≥3 CTC) at FUP was significantly associated with short recurrence-free survival (<i>p</i> = 0.002). Furthermore, detection of RARRES1 positive CTCs was indicative of an even earlier relapse after surgery (<i>p</i> = 0.001). Conclusions: CTC detection in resected PDAC patients during FUP is associated with a worse prognosis, and RARRES1 expression might identify an aggressive subtype of CTCs that deserves further investigation. |
| first_indexed | 2024-03-10T00:30:40Z |
| format | Article |
| id | doaj.art-89f2dead1d56422ebc50765b1bc64f49 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:30:40Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-89f2dead1d56422ebc50765b1bc64f492023-11-23T15:26:43ZengMDPI AGCancers2072-66942022-09-011418440510.3390/cancers14184405Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma PatientsChristine Nitschke0Benedikt Markmann1Marie Tölle2Jolanthe Kropidlowski3Yassine Belloum4Mara R. Goetz5Hartmut Schlüter6Marcel Kwiatkowski7Marianne Sinn8Jakob Izbicki9Klaus Pantel10Cenap Güngör11Faik G. Uzunoglu12Harriet Wikman13Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of Biochemistry and Center for Molecular Biosciences (CMBI), Leopold-Franzens University Innsbruck, 6020 Innsbruck, AustriaII. Medical Clinic and Polyclinic (Oncology), University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyBackground: In pancreatic ductal adenocarcinoma (PDAC), the characterization of circulating tumor cells (CTCs) opens new insights into cancer metastasis as the leading cause of cancer-related death. Here, we focused on the expression of retinoic acid receptor responder 1 (RARRES1) on CTCs as a novel marker for treatment failure and early relapse. Methods: The stable isotope labeling of amino acids in cell culture (SILAC)—approach was applied for identifying and quantifying new biomarker proteins in PDAC cell lines HPDE and its chemoresistant counterpart, L3.6pl-Res. Fifty-five baseline and 36 follow-up (FUP) peripheral blood samples were processed via a marker-independent microfluidic-based CTC detection approach using RARRES1 as an additional marker. Results: SILAC-based proteomics identified RARRES1 as an abundantly expressed protein in more aggressive chemoresistant PDAC cells. At baseline, CTCs were detected in 25.5% of all PDAC patients, while FUP analysis (median: 11 months FUP) showed CTC detection in 45.5% of the resected patients. CTC positivity (≥3 CTC) at FUP was significantly associated with short recurrence-free survival (<i>p</i> = 0.002). Furthermore, detection of RARRES1 positive CTCs was indicative of an even earlier relapse after surgery (<i>p</i> = 0.001). Conclusions: CTC detection in resected PDAC patients during FUP is associated with a worse prognosis, and RARRES1 expression might identify an aggressive subtype of CTCs that deserves further investigation.https://www.mdpi.com/2072-6694/14/18/4405liquid biopsycirculating tumor cellsRARRES1pancreatic ductal adenocarcinomabiomarker |
| spellingShingle | Christine Nitschke Benedikt Markmann Marie Tölle Jolanthe Kropidlowski Yassine Belloum Mara R. Goetz Hartmut Schlüter Marcel Kwiatkowski Marianne Sinn Jakob Izbicki Klaus Pantel Cenap Güngör Faik G. Uzunoglu Harriet Wikman Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma Patients Cancers liquid biopsy circulating tumor cells RARRES1 pancreatic ductal adenocarcinoma biomarker |
| title | Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma Patients |
| title_full | Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma Patients |
| title_fullStr | Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma Patients |
| title_full_unstemmed | Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma Patients |
| title_short | Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma Patients |
| title_sort | characterization of rarres1 expression on circulating tumor cells as unfavorable prognostic marker in resected pancreatic ductal adenocarcinoma patients |
| topic | liquid biopsy circulating tumor cells RARRES1 pancreatic ductal adenocarcinoma biomarker |
| url | https://www.mdpi.com/2072-6694/14/18/4405 |
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