Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jan 24, 2021; 12(1): 13-30
Published online Jan 24, 2021. doi: 10.5306/wjco.v12.i1.13
Evolutionary model of brain tumor circulating cells: Cellular galaxy
Parvin Mehdipour, Firoozeh Javan, Morteza Faghih Jouibari, Mehdi Khaleghi, Masoud Mehrazin
Parvin Mehdipour, Firoozeh Javan, Department of Medical Genetics, Tehran University of Medical Sciences, School of Medicine, Tehran 1417613151, Tehran, Iran
Morteza Faghih Jouibari, Department of Neurosurgery, Shariati University Hospital, Tehran 1417613151, Tehran, Iran
Mehdi Khaleghi, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1417613151, Tehran, Iran
Masoud Mehrazin, Tehran University of Medical Science, Tehran 1417613151, Tehran, Iran
Author contributions: Mehdipour P designed the research and protocols, analyzed the data, and wrote the paper; Javan F performed the technical protocols; Jouibari MF, Khaleghi M, and Mehrazin M provided the samples and patient information.
Supported by Tehran University of Medical Sciences, Research deputy under project, No. 32208-30-04-95.
Institutional review board statement: The study was reviewed and approved by the [IR.TUMS.MEDICINE] Institutional Review Board, No. 1395.1893.
Conflict-of-interest statement: The author and co-authors have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Parvin Mehdipour, PhD, Professor, Department of Medical Genetics, Tehran University of Medical Sciences, School of Medicine, Tehran 1417613151, Tehran, Iran. mehdipor@tums.ac.ir
Received: July 29, 2020
Peer-review started: July 29, 2020
First decision: October 18, 2020
Revised: November 5, 2020
Accepted: November 28, 2020
Article in press: November 28, 2020
Published online: January 24, 2021
Processing time: 171 Days and 16.9 Hours
Abstract
BACKGROUND

Although circulating tumor cells (CTCs) have been the focus of consideration for a decade, a categorized cell-based diagnostic strategy is unavailable. The personalized management and complementary/analytical-strategy of data require an alphabetic guide. Therefore, we aimed to determine the behavior of CTCs in tumor and blood in order to provide the hypothetical-based agenda in the brain neoplasms. Exploring the protein expression (PE) using a single cell-based method would clarify the heterogeneity and diversity in tumor and blood, which are key events in the evolution in brain tumors. In fact, heterogeneity, diversity, and evolution are required for cancer initiation and progression.

AIM

To explore CTCs in brain tumors and blood cells and to assay intensity of PE through personalized insight.

METHODS

The focal population included 14 patients with meningioma, and four patients with metastatic brain tumors (T). PE was assayed by immunofluorescence in tumors cells and CTCs in 18 patients with brain tumors. Ratio test was applied between the T cells and CTCs in tumor tissue and in vascular system. T/CTC ratio-based classification of PE in macrophage chemoattractant chemokine ligand 2 (CCL2), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), CD133, cyclin E, neurofilament marker, cytokeratin 19, and leukocyte common antigen (CD45) were investigated.

RESULTS

Total analyzed cells ranged between 10794-92283 for tumor cells and between 117-2870 for CTCs. Characteristics of histopathologic and status of an ataxia-telangiectasia mutated polymorphism (D1853N) in 18 patients affected with brain tumors were also provided. The course of evolution and metastatic event relied on the elevated protein expression in CTCs, which could be considered as a prognostic value. Diverse protein expression of the migrated cells into the blood stream and the tumor was indicative of the occurrence of evolution. Besides, the harmonic co-expression between CCL2/EGF and CCL2/VEGF could facilitate the tumor progression including the metastatic event. Expression of these proteins in the migrated vasculature and into the buccal tissue offered a non-invasive follow-up detection in neoplastic disorders. PE-exploration of neurofilament marker/CD133/VEGF of the CTCs in meningioma and cytokeratin 19/CD45/ cyclin E in the patients with metastatic brain tumor would clarify the tumor biology of the brain neoplastic disorders.

CONCLUSION

The alphabetical base of the evolutionary mechanisms relies on dual-, triple-, and multi-models with diverse intensity of expression. In fact, cross-talk between initiative and the complementary channels defines the evolutionary insight in cancer. A diverse-model of protein expression, including low, medium, and high intensity, is the key requirement for the completed model. The cluster of cells with diverse expression and remarkable co-expression between CCL2/EGF/VEGF and NM/CD133/VEGF in CTCs may be indicative of probable invasiveness of the tumor. Furthermore, the mode of cytokeratin-19+/CD45- can be traced in the metastatic patients.

Keywords: Circulating tumor cells; Brain tumor; Protein expression; Personalized; Somatic/circulating tumor cell evolution; Metastasis

Core Tip: The present data revealed that a classified/functional/individualized cell-based preventive and therapeutic strategy is required for the cancer management. An interaction between chemoattractant chemokine ligand 2/epidermal growth factor/vascular endothelial growth factor is an influential and key utility in the approach of cancer cells. Tracing the tumor/circulating tumor cells evolution will facilitate the estimation of functional alterations in blood stream as a model to predict the probable initiative step for metastasis, formulating the progressive status of disease and by planning for a translational/personalized management. Finally, heterogeneity and diversity may minimize the severity of disease.