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Poster Display session 1

5116 - Characterization of lung tumorspheres reveals cancer stem-like cells potential targets and prognostic markers in non-small cell lung cancer

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Alejandro Herreros Pomares

Citation

Annals of Oncology (2019) 30 (suppl_5): v585-v590. 10.1093/annonc/mdz258

Authors

A. Herreros Pomares1, E. Jantus-Lewintre2, S. Calabuig-Fariñas3, J.D. de-Maya-Girones4, R. Lucas5, A. Blasco6, R. Guijarro7, M. Martorell8, E. Escorihuela1, S. Alonso9, M.D. Chiara10, E. Duréndez1, C. Gandia4, R. Sirera11, R. Farràs4, C. Camps12

Author affiliations

  • 1 Molecular Oncology Laboratory-ciberonc, Fundación de Investigación Hospital General Universitario de Valencia, 46014 - Valencia/ES
  • 2 Department Of Biotechnology, Universidad Politécnica De Valencia, Molecular Oncology Laboratory-CIBERONC, Fundación de Investigación Hospital General Universitario de Valencia, 46014 - Valencia/ES
  • 3 Department Of Pathology, Universitat De València, Molecular Oncology Laboratory-CIBERONC, Fundación de Investigación Hospital General Universitario de Valencia, 46014 - Valencia/ES
  • 4 Oncogenic Signalling Laboratory, Centro de Investigación Príncipe Felipe, 46012 - Valencia/ES
  • 5 Department Of History Of Science And Documentation, Universitat de València, Valencia/ES
  • 6 Department Of Medical Oncology-ciberonc, Hospital General Universitario de Valencia, Valencia/ES
  • 7 Department Of Thoracic Surgery-ciberonc, Hospital General Universitario de Valencia, Valencia/ES
  • 8 Department Of Pathology, Hospital General Universitario de Valencia, Valencia/ES
  • 9 Program Of Predictive And Personalized Medicine Of Cancer, Institut de Reserca Germans Trias i Pujol (PMPPC-IGTP), Badalona/ES
  • 10 Institute Of Sanitary Research Of Asturias-ciberonc, Hospital Central de Asturias, Oviedo/ES
  • 11 Department Of Biotechnology-ciberonc, Universidad Politécnica de Valencia, Valencia/ES
  • 12 Department Of Medical Oncology, Hospital General Universitario De Valencia; Department Of Medicine, Hospital General Universitario De Valencia, Molecular Oncology Laboratory-CIBERONC, Fundación de Investigación Hospital General Universitario de Valencia, 46014 - Valencia/ES

Resources

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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.

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