Biomarkers in Liquid Biopsies for Prediction of Early Liver Metastases in Pancreatic Cancer

Anne Sophie Mehdorn; Timo Gemoll; Hauke Busch; Katharina Kern; Silje Beckinger; Tina Daunke; Christoph Kahlert; Faik G. Uzunoglu; Alexander Hendricks; Florian Buertin; Uwe A. Wittel; Yoshiaki Sunami; Christoph Röcken; Thomas Becker; Susanne Sebens

doi:10.3390/cancers14194605

Biomarkers in Liquid Biopsies for Prediction of Early Liver Metastases in Pancreatic Cancer

Anne Sophie Mehdorn, Timo Gemoll, Hauke Busch, Katharina Kern, Silje Beckinger, Tina Daunke, Christoph Kahlert, Faik G. Uzunoglu, Alexander Hendricks, Florian Buertin, Uwe A. Wittel, Yoshiaki Sunami, Christoph Röcken, Thomas Becker, Susanne Sebens^*

^*Korrespondierende/r Autor/-in für diese Arbeit

8 Zitate (Scopus)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies with poor survival rates. Only 20% of the patients are eligible for R0-surgical resection, presenting with early relapses, mainly in the liver. PDAC patients with hepatic metastases have a worse outcome compared to patients with metastases at other sites. Early detection of hepatic spread bears the potential to improve patient outcomes. Thus, this study sought for serum-based perioperative biomarkers allowing discrimination of early (EHMS ≤ 12 months) and late hepatic metastatic spread (LHMS > 12 months). Serum samples from 83 resectable PDAC patients were divided into EHMS and LHMS and analyzed for levels of inflammatory mediators by LEGENDplex^TM, which was validated and extended by Olink^® analysis. CA19-9 serum levels served as control. Results were correlated with clinicopathological data. While serum CA19-9 levels were comparable, Olink^® analysis confirmed distinct differences between both groups. It revealed significantly elevated levels of factors involved in chemotaxis and migration of immune cells, immune activity, and cell growth in serum of LHMS-patients. Overall, Olink^® analysis identified a comprehensive biomarker panel in serum of PDAC patients that could provide the basis for predicting LHMS. However, further studies with larger cohorts are required for its clinical translation.

Originalsprache	Englisch
Aufsatznummer	4605
Zeitschrift	Cancers
Jahrgang	14
Ausgabenummer	19
ISSN	2072-6694
DOIs	https://doi.org/10.3390/cancers14194605
Publikationsstatus	Veröffentlicht - 10.2022

Fördermittel

We thank Liane Carstensen, Sandra Ussat, Maike Witt-Ramdohr, Bianca Zinke, Heike Polster, Stephanie Mewes and Julia Wilking for their excellent technical support. We thank the biobank of Comprehensive Cancer Centre North (BMB-CCC) and Biobanks of the other centers participating for providing blood samples and clinical data for this study. The BMB-CCC is a member of the PopGen 2.0 Biobanking Network (P2N) Kiel and was funded by the German Federal Ministry of Education and Research (BMBF grant 01EY1103). This research was funded by the Medical Faculty of Kiel University (A.-S.M.) and the Deutsche Krebshilfe (AZ 70112935, S.S.). The BMB-CCC was funded by the German Federal Ministry of Education and Research (BMBF grant 01EY1103).

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Profilbereich: Lübeck Integrated Oncology Network (LION)

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10.3390/cancers14194605

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Mehdorn, A. S., Gemoll, T., Busch, H., Kern, K., Beckinger, S., Daunke, T., Kahlert, C., Uzunoglu, F. G., Hendricks, A., Buertin, F., Wittel, U. A., Sunami, Y., Röcken, C., Becker, T., & Sebens, S. (2022). Biomarkers in Liquid Biopsies for Prediction of Early Liver Metastases in Pancreatic Cancer. Cancers, 14(19), Artikel 4605. https://doi.org/10.3390/cancers14194605

@article{27503d2737f248628b8a683fb1282019,

title = "Biomarkers in Liquid Biopsies for Prediction of Early Liver Metastases in Pancreatic Cancer",

abstract = "Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies with poor survival rates. Only 20\% of the patients are eligible for R0-surgical resection, presenting with early relapses, mainly in the liver. PDAC patients with hepatic metastases have a worse outcome compared to patients with metastases at other sites. Early detection of hepatic spread bears the potential to improve patient outcomes. Thus, this study sought for serum-based perioperative biomarkers allowing discrimination of early (EHMS ≤ 12 months) and late hepatic metastatic spread (LHMS > 12 months). Serum samples from 83 resectable PDAC patients were divided into EHMS and LHMS and analyzed for levels of inflammatory mediators by LEGENDplexTM, which was validated and extended by Olink{\textregistered} analysis. CA19-9 serum levels served as control. Results were correlated with clinicopathological data. While serum CA19-9 levels were comparable, Olink{\textregistered} analysis confirmed distinct differences between both groups. It revealed significantly elevated levels of factors involved in chemotaxis and migration of immune cells, immune activity, and cell growth in serum of LHMS-patients. Overall, Olink{\textregistered} analysis identified a comprehensive biomarker panel in serum of PDAC patients that could provide the basis for predicting LHMS. However, further studies with larger cohorts are required for its clinical translation.",

author = "Mehdorn, \{Anne Sophie\} and Timo Gemoll and Hauke Busch and Katharina Kern and Silje Beckinger and Tina Daunke and Christoph Kahlert and Uzunoglu, \{Faik G.\} and Alexander Hendricks and Florian Buertin and Wittel, \{Uwe A.\} and Yoshiaki Sunami and Christoph R{\"o}cken and Thomas Becker and Susanne Sebens",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = oct,

doi = "10.3390/cancers14194605",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

number = "19",

}

TY - JOUR

T1 - Biomarkers in Liquid Biopsies for Prediction of Early Liver Metastases in Pancreatic Cancer

AU - Mehdorn, Anne Sophie

AU - Gemoll, Timo

AU - Busch, Hauke

AU - Kern, Katharina

AU - Beckinger, Silje

AU - Daunke, Tina

AU - Kahlert, Christoph

AU - Uzunoglu, Faik G.

AU - Hendricks, Alexander

AU - Buertin, Florian

AU - Wittel, Uwe A.

AU - Sunami, Yoshiaki

AU - Röcken, Christoph

AU - Becker, Thomas

AU - Sebens, Susanne

PY - 2022/10

Y1 - 2022/10

N2 - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies with poor survival rates. Only 20% of the patients are eligible for R0-surgical resection, presenting with early relapses, mainly in the liver. PDAC patients with hepatic metastases have a worse outcome compared to patients with metastases at other sites. Early detection of hepatic spread bears the potential to improve patient outcomes. Thus, this study sought for serum-based perioperative biomarkers allowing discrimination of early (EHMS ≤ 12 months) and late hepatic metastatic spread (LHMS > 12 months). Serum samples from 83 resectable PDAC patients were divided into EHMS and LHMS and analyzed for levels of inflammatory mediators by LEGENDplexTM, which was validated and extended by Olink® analysis. CA19-9 serum levels served as control. Results were correlated with clinicopathological data. While serum CA19-9 levels were comparable, Olink® analysis confirmed distinct differences between both groups. It revealed significantly elevated levels of factors involved in chemotaxis and migration of immune cells, immune activity, and cell growth in serum of LHMS-patients. Overall, Olink® analysis identified a comprehensive biomarker panel in serum of PDAC patients that could provide the basis for predicting LHMS. However, further studies with larger cohorts are required for its clinical translation.

AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies with poor survival rates. Only 20% of the patients are eligible for R0-surgical resection, presenting with early relapses, mainly in the liver. PDAC patients with hepatic metastases have a worse outcome compared to patients with metastases at other sites. Early detection of hepatic spread bears the potential to improve patient outcomes. Thus, this study sought for serum-based perioperative biomarkers allowing discrimination of early (EHMS ≤ 12 months) and late hepatic metastatic spread (LHMS > 12 months). Serum samples from 83 resectable PDAC patients were divided into EHMS and LHMS and analyzed for levels of inflammatory mediators by LEGENDplexTM, which was validated and extended by Olink® analysis. CA19-9 serum levels served as control. Results were correlated with clinicopathological data. While serum CA19-9 levels were comparable, Olink® analysis confirmed distinct differences between both groups. It revealed significantly elevated levels of factors involved in chemotaxis and migration of immune cells, immune activity, and cell growth in serum of LHMS-patients. Overall, Olink® analysis identified a comprehensive biomarker panel in serum of PDAC patients that could provide the basis for predicting LHMS. However, further studies with larger cohorts are required for its clinical translation.

UR - https://www.scopus.com/pages/publications/85139945069

U2 - 10.3390/cancers14194605

DO - 10.3390/cancers14194605

M3 - Journal articles

AN - SCOPUS:85139945069

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 19

M1 - 4605

ER -

Biomarkers in Liquid Biopsies for Prediction of Early Liver Metastases in Pancreatic Cancer

Abstract

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