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Article

Detyrosinated α-Tubulin, Vimentin and PD-L1 in Circulating Tumor Cells (CTCs) Isolated from Non-Small Cell Lung Cancer (NSCLC) Patients

by
Spyridoula D. Katsarou
1,2,3,
Ippokratis Messaritakis
4,
Anastasia Voumvouraki
3,
Stavros Kakavogiannis
1,
Athanasios Κotsakis
5,6,
Saad Alkahtani
2,3,
Christos Stournaras
3,
Stuart S. Martin
7,
Vassilis Georgoulias
6 and
Galatea Kallergi
1,*
1
Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, 26504 Patras, Greece
2
Department of Zoology, Science College, King Saud University, Riyadh 11451, Saudi Arabia
3
Department of Biochemistry, Medical School, University of Crete, 71003 Heraklion, Greece
4
Laboratory of Translational Oncology, Medical School, University of Crete, 71003 Heraklion, Greece
5
Department of Medical Oncology, University General Hospital of Larisa, 41334 Larisa, Greece
6
Hellenic Oncology Research Group (HORG), 11526 Athens, Greece
7
Department of Physiology, School of Medicine, University of Maryland, Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2022, 12(2), 154; https://doi.org/10.3390/jpm12020154
Submission received: 7 November 2021 / Revised: 7 January 2022 / Accepted: 17 January 2022 / Published: 25 January 2022
(This article belongs to the Special Issue Precision Medicine for Immunology and Immunogenetics)

Abstract

Upregulation of Vimentin (VIM), alpha-Tubulin (TUB) and Detyrosinated tubulin (GLU) in circulating tumor cells (CTCs) derived from breast cancer patients is related to poor prognosis. In the current study we evaluated for the first time, these cytoskeletal proteins in sixty Non-Small Cell Lung Cancer (NSCLC) patients’ CTCs (33 treatment-naïve and 27 pre-treated). Samples were isolated using the ISET platform and stained with a pancytokeratin (CK)/CD45/TUB, CK/GLU/VIM and CK/programmed death ligand 1 (PD-L1) combination of antibodies. Subsequently, slides were analyzed using confocal laser scanning microscopy. CTCs were detected in 86.7% of the patients. CTCs with TUB expression were identified in 65.4% (34/52) of the CK (+)-patients. GLU, VIM and PD-L1 were also evaluated. The frequency of the observed phenotypes was as follow: (CK+/GLU−/VIM−): 35.2%, (CK+/GLU+/VIM+): 63.0%, (CK+/GLU+/VIM−): 16.7%, (CK+/GLU−/VIM+): 72.2%, (CK+/PD-L1−): 75% and (CK+/PD-L1+): 55%. The OS was significantly decreased in patients with high GLU (3.8 vs. 7.9 months; p = 0.018) and/or high VIM (3.2 vs. 7.1 months; p = 0.029) expression in their CTCs. PD-L1 was also related to OS (3.4 vs. 7.21 months; p = 0.035). Moreover, TUB-high and TUB-low expression in CTCs inversely influenced patients’ OS as independent prognostic factors (p = 0.041 and p = 0.009). The current study revealed that TUB, GLU, VIM and PD-L1 were overexpressed in CTCs from NSCLC patients. Furthermore, the presence of GLU, VIM-positive and PD-L1 in CTCs is potentially related to patients’ outcomes.
Keywords: CTCs; lung cancer; alpha-tubulin; detyrosinated α-tubulin; vimentin; PD-L1; metastasis CTCs; lung cancer; alpha-tubulin; detyrosinated α-tubulin; vimentin; PD-L1; metastasis

Share and Cite

MDPI and ACS Style

Katsarou, S.D.; Messaritakis, I.; Voumvouraki, A.; Kakavogiannis, S.; Κotsakis, A.; Alkahtani, S.; Stournaras, C.; Martin, S.S.; Georgoulias, V.; Kallergi, G. Detyrosinated α-Tubulin, Vimentin and PD-L1 in Circulating Tumor Cells (CTCs) Isolated from Non-Small Cell Lung Cancer (NSCLC) Patients. J. Pers. Med. 2022, 12, 154. https://doi.org/10.3390/jpm12020154

AMA Style

Katsarou SD, Messaritakis I, Voumvouraki A, Kakavogiannis S, Κotsakis A, Alkahtani S, Stournaras C, Martin SS, Georgoulias V, Kallergi G. Detyrosinated α-Tubulin, Vimentin and PD-L1 in Circulating Tumor Cells (CTCs) Isolated from Non-Small Cell Lung Cancer (NSCLC) Patients. Journal of Personalized Medicine. 2022; 12(2):154. https://doi.org/10.3390/jpm12020154

Chicago/Turabian Style

Katsarou, Spyridoula D., Ippokratis Messaritakis, Anastasia Voumvouraki, Stavros Kakavogiannis, Athanasios Κotsakis, Saad Alkahtani, Christos Stournaras, Stuart S. Martin, Vassilis Georgoulias, and Galatea Kallergi. 2022. "Detyrosinated α-Tubulin, Vimentin and PD-L1 in Circulating Tumor Cells (CTCs) Isolated from Non-Small Cell Lung Cancer (NSCLC) Patients" Journal of Personalized Medicine 12, no. 2: 154. https://doi.org/10.3390/jpm12020154

APA Style

Katsarou, S. D., Messaritakis, I., Voumvouraki, A., Kakavogiannis, S., Κotsakis, A., Alkahtani, S., Stournaras, C., Martin, S. S., Georgoulias, V., & Kallergi, G. (2022). Detyrosinated α-Tubulin, Vimentin and PD-L1 in Circulating Tumor Cells (CTCs) Isolated from Non-Small Cell Lung Cancer (NSCLC) Patients. Journal of Personalized Medicine, 12(2), 154. https://doi.org/10.3390/jpm12020154

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