CD44+/EPCAM+ cells detect a subpopulation of ALDHhigh cells in human non-small cell lung cancer: A chance for targeting cancer stem cells?
Valentina Masciale, Giulia Grisendi, Federico Banchelli, Roberto D’Amico, Antonino Maiorana, Pamela Sighinolfi, Alessandro Stefani, Uliano Morandi, Massimo Dominici, Beatrice Aramini
Abstract
// Valentina Masciale 1 , * , Giulia Grisendi 2 , * , Federico Banchelli 3 , * , Roberto D’Amico 3 , Antonino Maiorana 4 , Pamela Sighinolfi 4 , Alessandro Stefani 1 , Uliano Morandi 1 , Massimo Dominici 2 , * and Beatrice Aramini 1 , * 1 Division of Thoracic Surgery, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy 2 Division of Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy 3 Center of Statistic, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy 4 Institute of Pathology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy * Co-first/last authors Correspondence to: Beatrice Aramini, email: [email protected] Keywords: immunophenotype; cancer stem cells; cancer stem-like cells; non-small cell lung cancer (NSCLC); target therapy Received: February 08, 2020     Accepted: April 03, 2020     Published: April 28, 2020 ABSTRACT Objectives: Several studies demonstrated that aldehyde dehydrogenase (ALDH) and CD44 are the most considered cancer stem cells (CSC) markers. However, a comparison between ALDH high cells and CD44+ cells have been previously described with no significant correlation. Indeed, the aim of the present research is to identify a superficial marker able to match with ALDH high cells population in freshly isolated human lung cancer cells. Materials and Methods: This cross-sectional study analyzed the expression of ALDH high/low cells and the positivity for CD44 and epithelium cell adhesion molecule (EPCAM) antigens in surgical lung cancer tissues. The main approach was a cytofluorimetric analysis of ALDH expression and positivity for CD44/EPCAM on primary cell population obtained from 23 patients harboring NSCLC. Results: There was a highly positive correlation between the expressions of ALDH high and CD44+/EPCAM+ cells, with a Pearson’s correlation coefficient equal to 0.69 (95% CI 0.39–0.86; P = 0.0002), and Spearman’s correlation coefficient equal to 0.52 ( P = 0.0124). The average paired difference between the expression of ALDH high and CD44+/EPCAM+ cells was very close to 0, being 0.1% (SD 2.5%); there was no difference between these subpopulations in terms of means (95% CI = –1.0; 1.2%, P = 0.8464). These results highlight a strong similarity between ALDH high and CD44+/EPCAM+ cells. Conclusions: Our study is the first attempt which identifies a high correlation between the ALDH high and the CD44+/EPCAM+ cells, thus suggesting the possibility to use this superficial marker for future target treatments against lung cancer stem cells.