Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide, with no precise method for early detection. Circulating tumor cells (CTCs) expressing the dynamic polarity of the cytoskeletal membrane protein, ezrin, have been proposed to...

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Main Authors: Ibrahim Büdeyri, Olaf Guckelberger, Elsie Oppermann, Dhruvajyoti Roy, Svenja Sliwinski, Felix Becker, Benjamin Struecker, Thomas J. Vogl, Andreas Pascher, Wolf O. Bechstein, Anna Lorentzen, Mathias Heikenwalder, Mazen A. Juratli
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Language:English
Published: MDPI AG 2024-12-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/1/6
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author Ibrahim Büdeyri
Olaf Guckelberger
Elsie Oppermann
Dhruvajyoti Roy
Svenja Sliwinski
Felix Becker
Benjamin Struecker
Thomas J. Vogl
Andreas Pascher
Wolf O. Bechstein
Anna Lorentzen
Mathias Heikenwalder
Mazen A. Juratli
author_facet Ibrahim Büdeyri
Olaf Guckelberger
Elsie Oppermann
Dhruvajyoti Roy
Svenja Sliwinski
Felix Becker
Benjamin Struecker
Thomas J. Vogl
Andreas Pascher
Wolf O. Bechstein
Anna Lorentzen
Mathias Heikenwalder
Mazen A. Juratli
author_sort Ibrahim Büdeyri
collection DOAJ
description Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide, with no precise method for early detection. Circulating tumor cells (CTCs) expressing the dynamic polarity of the cytoskeletal membrane protein, ezrin, have been proposed to play a crucial role in tumor progression and metastasis. This study investigated the diagnostic and prognostic potential of polarized circulating tumor cells (p-CTCs) in HCC patients. CTCs were isolated from the peripheral blood of 20 HCC patients and 18 patients with nonmalignant liver disease (NMLD) via an OncoQuick<sup>®</sup> kit and immunostained with Ezrin-Alexa Fluor 488<sup>®</sup>, CD146-PE, and CD45-APC. A fluorescence microscopy was then performed for analysis. The HCC group exhibited significantly higher levels of p-CTCs, with median values of 0.56 p-CTCs/mL, compared to 0.02 p-CTCs/mL (<i>p</i> = 0.03) in the NMLD group. CTCs were detected in 95% of the HCC patients, with a sensitivity of 95% and specificity of 89%. p-CTCs were present in 75% of the HCC patients, with a sensitivity of 75% and a specificity of 94%. Higher p-CTC counts were associated with the significantly longer overall survival in HCC patients (<i>p</i> = 0.05). These findings suggest that p-CTCs could serve as valuable diagnostic and prognostic markers for HCC. The incorporation of p-CTCs into diagnostic strategies could enhance therapeutic decision-making and improve patient outcomes.
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spelling doaj-art-3d3d01289d93423bac45bf24b9c8a45f2025-01-10T13:16:13ZengMDPI AGCells2073-44092024-12-01141610.3390/cells14010006Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular CarcinomaIbrahim Büdeyri0Olaf Guckelberger1Elsie Oppermann2Dhruvajyoti Roy3Svenja Sliwinski4Felix Becker5Benjamin Struecker6Thomas J. Vogl7Andreas Pascher8Wolf O. Bechstein9Anna Lorentzen10Mathias Heikenwalder11Mazen A. Juratli12Department of General, Visceral and Transplant Surgery, University Hospital Muenster, University of Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, GermanyDepartment of General, Visceral and Transplant Surgery, University Hospital Muenster, University of Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, GermanyDepartment of General, Visceral and Transplant Surgery, Frankfurt University Hospital, 60596 Frankfurt, GermanyDepartment of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USADepartment of General, Visceral and Transplant Surgery, Frankfurt University Hospital, 60596 Frankfurt, GermanyDepartment of General, Visceral and Transplant Surgery, University Hospital Muenster, University of Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, GermanyDepartment of General, Visceral and Transplant Surgery, University Hospital Muenster, University of Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, GermanyDepartment of Diagnostic and Interventional Radiology, Frankfurt University Hospital, Goethe University, 60596 Frankfurt, GermanyDepartment of General, Visceral and Transplant Surgery, University Hospital Muenster, University of Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, GermanyDepartment of General, Visceral and Transplant Surgery, Frankfurt University Hospital, 60596 Frankfurt, GermanyDepartment of Biomedicine, Aarhus University, 8200 Aarhus, DenmarkDivision of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDepartment of General, Visceral and Transplant Surgery, University Hospital Muenster, University of Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, GermanyHepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide, with no precise method for early detection. Circulating tumor cells (CTCs) expressing the dynamic polarity of the cytoskeletal membrane protein, ezrin, have been proposed to play a crucial role in tumor progression and metastasis. This study investigated the diagnostic and prognostic potential of polarized circulating tumor cells (p-CTCs) in HCC patients. CTCs were isolated from the peripheral blood of 20 HCC patients and 18 patients with nonmalignant liver disease (NMLD) via an OncoQuick<sup>®</sup> kit and immunostained with Ezrin-Alexa Fluor 488<sup>®</sup>, CD146-PE, and CD45-APC. A fluorescence microscopy was then performed for analysis. The HCC group exhibited significantly higher levels of p-CTCs, with median values of 0.56 p-CTCs/mL, compared to 0.02 p-CTCs/mL (<i>p</i> = 0.03) in the NMLD group. CTCs were detected in 95% of the HCC patients, with a sensitivity of 95% and specificity of 89%. p-CTCs were present in 75% of the HCC patients, with a sensitivity of 75% and a specificity of 94%. Higher p-CTC counts were associated with the significantly longer overall survival in HCC patients (<i>p</i> = 0.05). These findings suggest that p-CTCs could serve as valuable diagnostic and prognostic markers for HCC. The incorporation of p-CTCs into diagnostic strategies could enhance therapeutic decision-making and improve patient outcomes.https://www.mdpi.com/2073-4409/14/1/6hepatocellular carcinomacirculating tumor cellspolarizationcancersingle-cell polaritypersonalized diagnosis and therapy
spellingShingle Ibrahim Büdeyri
Olaf Guckelberger
Elsie Oppermann
Dhruvajyoti Roy
Svenja Sliwinski
Felix Becker
Benjamin Struecker
Thomas J. Vogl
Andreas Pascher
Wolf O. Bechstein
Anna Lorentzen
Mathias Heikenwalder
Mazen A. Juratli
Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular Carcinoma
Cells
hepatocellular carcinoma
circulating tumor cells
polarization
cancer
single-cell polarity
personalized diagnosis and therapy
title Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular Carcinoma
title_full Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular Carcinoma
title_fullStr Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular Carcinoma
title_full_unstemmed Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular Carcinoma
title_short Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular Carcinoma
title_sort ezrin polarization as a diagnostic marker for circulating tumor cells in hepatocellular carcinoma
topic hepatocellular carcinoma
circulating tumor cells
polarization
cancer
single-cell polarity
personalized diagnosis and therapy
url https://www.mdpi.com/2073-4409/14/1/6
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