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

Cells. 2024 Dec 25;14(1):6. doi: 10.3390/cells14010006.

Abstract

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® kit and immunostained with Ezrin-Alexa Fluor 488®, 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 (p = 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 (p = 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.

Keywords: cancer; circulating tumor cells; ezrin; hepatocellular carcinoma; liver surgery; personalized diagnosis and therapy; polarization; single-cell polarity.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / metabolism
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Polarity
  • Cytoskeletal Proteins* / blood
  • Cytoskeletal Proteins* / metabolism
  • Female
  • Humans
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating* / metabolism
  • Neoplastic Cells, Circulating* / pathology
  • Prognosis

Substances

  • ezrin
  • Biomarkers, Tumor
  • Cytoskeletal Proteins

Grants and funding

This work was supported by Rudolf Geißendörfer-Stiftung, in the form of a grant awarded to M.A.J. (2015); Frankfurter Forschungsfoerderung, in the form of a grant awarded to M.A.J. [FFF 2017]; and B. Braun-Stiftung, in the form of a grant awarded to M.A.J. (2018). We acknowledge the support from the Open Access Publication Fund of the University of Muenster. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.