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
3158 - Tobacco Retail Access and Tobacco Cessation Among Head and Neck Cancer (HNC) Survivors
Presenter: Lawson Eng
Session: Poster Display session 1
Resources:
Abstract
5511 - ASSERT: A Prospective, Observational Study Measuring Sodium Improvement and Outcomes in Patients Treated for Moderate to Severe Hyponatremia Secondary to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in Italy (Lung Cancer Cohort)
Presenter: Rossana Berardi
Session: Poster Display session 1
Resources:
Abstract
3821 - Efficacy and safety of controlled ovarian stimulation with or without letrozole co-administration for fertility preservation: A systematic review and meta-analysis.
Presenter: Benedetta Bonardi
Session: Poster Display session 1
Resources:
Abstract
2168 - Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy
Presenter: Tineke Vandenbroucke
Session: Poster Display session 1
Resources:
Abstract
5855 - Update of the registry of young women with cancer by the International Network of Cancer, Infertility and Pregnancy
Presenter: Charlotte Maggen
Session: Poster Display session 1
Resources:
Abstract
5156 - Erectile dysfunction in patients with metastatic renal cell carcinoma
Presenter: Ilya Tsimafeyeu
Session: Poster Display session 1
Resources:
Abstract
4992 - Exercise level, interest and preferences in cancer patients.
Presenter: Alice Avancini
Session: Poster Display session 1
Resources:
Abstract
3427 - Filling the Gaps in Informed Consent for Advanced Cancer Patients considering Phase 1 Oncology Trials - an in-depth Qualitative Study of Key Stakeholders at a large United Kingdom Phase 1 unit
Presenter: Abhijit Pal
Session: Poster Display session 1
Resources:
Abstract
3537 - Breast Cancer Patients’ Quality of Life: Real World Data
Presenter: Thanos Kosmidis
Session: Poster Display session 1
Resources:
Abstract
4761 - High-sensitivity troponin as a cardiotoxicity biomarker in breast cancer treatment
Presenter: Joana Simões
Session: Poster Display session 1
Resources:
Abstract