Abstract 5116
Background
Non-small cell lung cancer (NSCLC) is the first cause of death cancer-related worldwide mainly due to high therapeutic resistance. This resistance is related to cancer stem-like cells (CSCs), for which the identification of targets and markers is still ongoing.
Methods
Primary cultures from 8 NSCLC patients were established as tumorspheres and as monolayers. CSCs properties were tested for both conditions in vitro and in vivo. The expression of 50 CSCs-related genes was assessed by RTqPCR and proteins of significantly overexpressed genes were examined by immunoblot and immunofluorescence. The prognostic role of these genes was analyzed in a cohort of 661 NSCLC patients from TCGA and validated in an independent cohort of 114 lung adenocarcinoma (ADC) patients.
Results
Tumorspheres exhibited self-renewal, unlimited exponential growth, drug resistance, great invasion and differentiation capacities in vitro and higher tumorigenic potential than monolayers in vivo. 17 genes were significantly overexpressed in tumorspheres, being NANOG, NOTCH3, CD44, CDKN1A, SNAI1, and ITGA6 the major contributors to distinguish them from adherent cells. Proteins encoded by these genes showed differential localization and expression patterns in ADC tumorspheres. The expression of CDKN1A, SNAI1 and ITGA6 was associated to prognosis, so a score was built based on their regression coefficients from a multivariate model. TCGA patients with high CSCs score show shorter OS in the entire cohort [37.7 vs. 60.4 mo., p = 0.001] and the ADC subcohort [36.6 vs. 53.5 mo., p = 0.003]. Multivariate analysis indicated that this score is an independent biomarker of prognosis for OS in the entire cohort from TCGA [HR: 1.498; 95% CI, 1.167-1.922; p = 0.001] and the ADC subcohort [HR: 1.869; 95% CI, 1.275-2.738; p = 0.001]. The prognostic value is confirmed in an independent cohort of 114 lung adenocarcinoma patients OS (42.90 vs. NR mo, p = 0.020).
Conclusions
Lung tumorspheres are a useful method for CSCs enrichment. Elevated expression of CDKN1A, SNAI1 and ITGA6 genes is associated with worse prognosis in NSCLC. Funded by CB16/12/00350 from CIBEROnc, PI12-02838, and PI15-00753 from ISCIII, Fundacion Arnal Planelles and Domingo Martínez.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fundación de Investigación Hospital General de Valencia.
Funding
CIBEROnc, Instituto de Salud Carlos III; Fundacion Arnal Planelles and Domingo Martínez.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4925 - Prognostic role of CD73 in metastatic Non Small Cell Lung Cancer according to the presence of driver alterations
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract
785 - JAK-STAT inhibitor overcomes interferon γ-reduced, NK cell-mediated cytotoxicity in non-small-cell lung cancer cells
Presenter: Riki Okita
Session: Poster Display session 1
Resources:
Abstract
2326 - Low LATS2 expression is associated with poor prognosis in non small cell lung cancer
Presenter: Si-hyong Jang
Session: Poster Display session 1
Resources:
Abstract
5960 - Application of ESCAT and OncoKB scales in Liquid biopsy (LB) in Advanced NSCLC patients (pts): Is it feasible and reliable?
Presenter: Michael McCusker
Session: Poster Display session 1
Resources:
Abstract
4855 - IDH1R132H mutation induces a less aggressive phenotype of glioma cells and affects the radiosensitivity by interacting with Wnt/β-catenin signaling
Presenter: Xuetao Han
Session: Poster Display session 1
Resources:
Abstract
2641 - Impact of Angiopoietin-2 on glioblastoma response to combined chemo-radiotherapy
Presenter: Charly Helaine
Session: Poster Display session 1
Resources:
Abstract
5743 - The Discovery of RNA-aptamers That Selectively Bind and Inhibit Glioblastoma Stem Cells by targeting EphA2
Presenter: Alessandra Affinito
Session: Poster Display session 1
Resources:
Abstract
4160 - Impact of tumor reoxygenation by nanoparticles on Tumor Associated Macrophages (TAMs)
Presenter: Aurélie Ferré
Session: Poster Display session 1
Resources:
Abstract
2474 - Prognostic significance of c-Rel/p50 heterodimer in the tumor microenvironment of uveal melanoma
Presenter: Seema Kashyap
Session: Poster Display session 1
Resources:
Abstract
1769 - Synergistic role of BAP1 and DNA damage response pathway in uveal melanoma and its prognostic significance.
Presenter: JAYANTI JHA
Session: Poster Display session 1
Resources:
Abstract