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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.
Highlights
This article is an open access articleLung cancer is the second most commonly diagnosed cancer, both in men and women and still remains the leading cause of cancer-related deaths worldwide [1]
It is well known that the presence of circulating tumor cells (CTCs) in the bloodstream is a poor prognostic factor for a number of cancer types, including Non-Small CellLung Cancer (NSCLC) [4,5,6]
In the TUB positive cells, microtentacles of tubulin participate in the communication between cancer cells and normal peripheral blood mononuclear cells (PBMCs)
Summary
This article is an open access articleLung cancer is the second most commonly diagnosed cancer, both in men and women and still remains the leading cause of cancer-related deaths worldwide [1]. Lung Cancer (NSCLC) accounts for 85% of all lung cancer subtypes. It is associated with high mortality because usually, the initial diagnosis occurs when the disease is already locally advanced or with distant metastasis [2,3]. It is well known that the presence of circulating tumor cells (CTCs) in the bloodstream is a poor prognostic factor for a number of cancer types, including NSCLC [4,5,6]. Knowing the heterogeneity of primary tumors even in patients with the same histologic subtype, CTCs could provide useful information regarding the metastatic potential of different subclones [13]
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