Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma Patients.

RARRES1 biomarker circulating tumor cells liquid biopsy pancreatic ductal adenocarcinoma

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
10 Sep 2022
Historique:
received: 07 07 2022
revised: 04 08 2022
accepted: 01 09 2022
entrez: 23 9 2022
pubmed: 24 9 2022
medline: 24 9 2022
Statut: epublish

Résumé

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. 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. 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 ( 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.

Sections du résumé

BACKGROUND 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 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 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 (
CONCLUSIONS 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.

Identifiants

pubmed: 36139565
pii: cancers14184405
doi: 10.3390/cancers14184405
pmc: PMC9497091
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Erich Und Gertrud Roggenbuck Stiftung
ID : 2072/100

Références

Cancer Discov. 2021 Apr;11(4):858-873
pubmed: 33811121
Cancer Res. 2011 Jul 15;71(14):5009-19
pubmed: 21632553
Eur J Surg Oncol. 2017 Jun;43(6):1050-1055
pubmed: 28233633
Int J Mol Sci. 2021 Jun 29;22(13):
pubmed: 34209696
ESMO Open. 2021 Dec;6(6):100299
pubmed: 34839105
Mol Oncol. 2016 Mar;10(3):374-94
pubmed: 26897752
Front Cell Dev Biol. 2022 May 26;10:918795
pubmed: 35712663
Int J Cancer. 2012 Sep 15;131(6):E897-904
pubmed: 22573467
Int J Mol Sci. 2022 Jan 31;23(3):
pubmed: 35163592
Clin Cancer Res. 2018 Jun 15;24(12):2844-2850
pubmed: 29559560
Nat Cancer. 2022 Mar;3(3):272-286
pubmed: 35352061
Am J Pathol. 2019 Jan;189(1):71-81
pubmed: 30558725
Cancers (Basel). 2019 Oct 26;11(11):
pubmed: 31717773
Cancers (Basel). 2021 Jan 27;13(3):
pubmed: 33513877
Clin Chem. 2021 Mar 31;67(4):631-641
pubmed: 33491069
Oral Oncol. 2008 Apr;44(4):400-6
pubmed: 17689134
Asian Pac J Cancer Prev. 2014;15(15):6015-20
pubmed: 25124566
Am J Transl Res. 2019 Sep 15;11(9):5655-5663
pubmed: 31632537
Ann Surg. 2016 Dec;264(6):1073-1081
pubmed: 26756760
Cancers (Basel). 2019 Oct 26;11(11):
pubmed: 31717747
Tumour Biol. 2014 Mar;35(3):2473-80
pubmed: 24218336
Cancers (Basel). 2020 Feb 13;12(2):
pubmed: 32069934
Oncotarget. 2019 Feb 26;10(17):1606-1624
pubmed: 30899431
Cell. 2012 Jan 20;148(1-2):349-61
pubmed: 22265420
Nat Rev Clin Oncol. 2019 Jul;16(7):409-424
pubmed: 30796368
Int J Cancer. 2016 Jun 15;138(12):2894-904
pubmed: 26789903
Crit Rev Clin Lab Sci. 2014 Jun;51(3):160-71
pubmed: 24641350
PLoS One. 2018 Dec 17;13(12):e0208756
pubmed: 30557378
Mol Oncol. 2019 Aug;13(8):1623-1650
pubmed: 31243883
Br J Pharmacol. 2014 Feb;171(4):849-58
pubmed: 24024905
Eur J Cancer. 2006 Mar;42(4):557-65
pubmed: 16426842

Auteurs

Christine Nitschke (C)

Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.
Mildred Scheel Cancer Career Center, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Benedikt Markmann (B)

Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Marie Tölle (M)

Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Jolanthe Kropidlowski (J)

Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Yassine Belloum (Y)

Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Mara R Goetz (MR)

Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Hartmut Schlüter (H)

Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Marcel Kwiatkowski (M)

Institute of Biochemistry and Center for Molecular Biosciences (CMBI), Leopold-Franzens University Innsbruck, 6020 Innsbruck, Austria.

Marianne Sinn (M)

II. Medical Clinic and Polyclinic (Oncology), University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Jakob Izbicki (J)

Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Klaus Pantel (K)

Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Cenap Güngör (C)

Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Faik G Uzunoglu (FG)

Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Harriet Wikman (H)

Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.

Classifications MeSH