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


ABSTRACT:

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 (p = 0.002). Furthermore, detection of RARRES1 positive CTCs was indicative of an even earlier relapse after surgery (p = 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.

SUBMITTER: Nitschke C 

PROVIDER: S-EPMC9497091 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Nitschke Christine C   Markmann Benedikt B   Tölle Marie M   Kropidlowski Jolanthe J   Belloum Yassine Y   Goetz Mara R MR   Schlüter Hartmut H   Kwiatkowski Marcel M   Sinn Marianne M   Izbicki Jakob J   Pantel Klaus K   Güngör Cenap C   Uzunoglu Faik G FG   Wikman Harriet H  

Cancers 20220910 18


<h4>Background</h4>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.<h4>Methods</h4>The stable isotope labeling of amino acids in cell culture (SILAC)-approach was applied for identifying and quantifying new bioma  ...[more]

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