New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells

Valentina Masciale; Federico Banchelli; Giulia Grisendi; Roberto D'Amico; Antonino Maiorana; Alessandro Stefani; Uliano Morandi; Massimo Dominici; Beatrice Aramini

doi:10.3389/fonc.2021.613198

New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells

Front Oncol. 2021 Mar 31:11:613198. doi: 10.3389/fonc.2021.613198. eCollection 2021.

Authors

Valentina Masciale¹, Federico Banchelli², Giulia Grisendi³, Roberto D'Amico², Antonino Maiorana⁴, Alessandro Stefani¹, Uliano Morandi¹, Massimo Dominici³, Beatrice Aramini¹

Affiliations

¹ Division of Thoracic Surgery, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
² Center of Statistic, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
³ Division of Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
⁴ Department of Medical and Surgical Sciences, Institute of Pathology, University of Modena and Reggio Emilia, Modena, Italy.

Abstract

Introduction: Lung cancer is one of the most common cancers in the world, causing over 1.7 million deaths in 2018. Thus far, no effective treatments against lung cancer for advanced stages have been found. For early stages, although surgery is considered the gold standard treatment, 30-55% of patients develop recurrence within the first 5 years of surgery. Our aim is to assess whether cancer stem cells (CSC) display overexpression of a pool of genes that were previously identified for adenocarcinoma recurrence in patients with early and locally advanced stages of non-small cell lung cancer (NSCLC).

Methods: This cross-sectional study was carried out by harvesting surgical tumor specimens obtained from patients harboring early (I-II) and locally advanced (IIIA) stages of NSCLC. For each patient, cell sorting was performed to identify and isolate the ALDH^high (CSC) and ALDH^low (cancer cells) populations. The mRNA expressions of 31 recurrence-related genes (target genes) in both ALDH^high and ALDH^low populations were then assessed and compared.

Results: Surgical specimens were obtained from 22 patients harboring NSCLC. Sixteen (51.6%) out of 31 recurrence-related genes were significantly overexpressed in ALDH^high cells in the early stages and 9 (29.0%) were overexpressed in the locally advanced stages of NSCLC. Overall, the relative mRNA expressions for these recurrence-related genes were higher in early-stage patients. The average fold change, considering all 31 recurrence-related genes together, was 4.5 (95% CI = 3.1-6.3) in early-stage patients and 1.6 (95% CI = 1.2-2.2) in locally advanced-stage patients.

Conclusions: Our study represents the first attempt toward identifying genes associated with recurrence that are overexpressed in cancer stem cells in patients with early and locally advanced stages of NSCLC. This finding may contribute to the identification of new target therapies tailored for NSCLC stages.

Keywords: cancer stem cells; early and advanced stage; gene expression; non-small cell lung cancer (NSCLC); target therapy.