Phenotypic Characterization of Circulating Tumor Cells Isolated from Non-Small and Small Cell Lung Cancer Patients

Argyro Roumeliotou; Evangelia Pantazaka; Anastasia Xagara; Foteinos-Ioannis Dimitrakopoulos; Angelos Koutras; Athina Christopoulou; Theodoros Kourelis; Nada H Aljarba; Saad Alkahtani; Filippos Koinis; Athanasios Kotsakis; Galatea Kallergi

doi:10.3390/cancers15010171

Phenotypic Characterization of Circulating Tumor Cells Isolated from Non-Small and Small Cell Lung Cancer Patients

Cancers (Basel). 2022 Dec 28;15(1):171. doi: 10.3390/cancers15010171.

Affiliations

¹ Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece.
² Laboratory of Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, Greece.
³ Division of Oncology, Department of Medicine, University Hospital, Medical School, University of Patras, 26504 Patras, Greece.
⁴ Oncology Unit, ST Andrews General Hospital of Patras, 26332 Patras, Greece.
⁵ Department of Medical Oncology, "Olympion" General Hospital, 26443 Patras, Greece.
⁶ Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
⁷ Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁸ Department of Medical Oncology, University General Hospital of Larissa, 41221 Larisa, Greece.

Abstract

In the present study, we evaluated the expression of JUNB and CXCR4 in circulating tumor cells (CTCs) of lung cancer patients and investigated whether these proteins have prognostic clinical relevance. Peripheral blood from 30 patients with non-small-cell lung cancer (NSCLC) was filtered using ISET membranes, and cytospins from 37 patients with small-cell lung cancer (SCLC) were analyzed using confocal and VyCAP microscopy. Both JUNB and CXCR4 were expressed in the vast majority of lung cancer patients. Interestingly, the phenotypic patterns differed between NSCLC and SCLC patients; the (CK+/JUNB+/CXCR4+) phenotype was present in 50% of NSCLC vs. 71% of SCLC patients. Similarly, the (CK+/JUNB+/CXCR4−) was present in 44% vs. 71%, the (CK+/JUNB−/CXCR4+) in 6% vs. 71%, and the (CK+/JUNB−/CXCR4−) phenotype in 38% vs. 84%. In NSCLC, the presence of ≥1 CTCs with the (CK+/JUNB+/CXCR4+) phenotype was associated with worse progression-free survival (PFS) (p = 0.007, HR = 5.21) while ≥2 with poorer overall survival (OS) (p < 0.001, HR = 2.16). In extensive stage SCLC patients, the presence of ≥4 CXCR4-positive CTCs was associated with shorter OS (p = 0.041, HR = 5.01). Consequently, JUNB and CXCR4 were expressed in CTCs from lung cancer patients, and associated with patients’ survival, underlying their key role in tumor progression.

Keywords: CXCR4; JUNB; circulating tumor cells; lung cancer; non-small-cell lung cancer; small-cell lung cancer.

Grants and funding

This research has been co-financed by the European Regional Development Fund of the European Union and Greek funds through the Operational Program Competitiveness Entrepreneurship and Innovation, under the call RESEARCH–CREATE–INNOVATE (project code: Τ2ΕDΚ-01562). This work was also funded by Researchers Supporting Project number (RSP2023R26), King Saud University, Riyadh, Saudi Arabia.