Abstract 1167P
Background
Critical pathways are shared between embryogenesis and cancer; but while the first is an organized and well-regulated process, the last is characterized by entropy. Several works have evaluated the potential of the embryonic microenvironment for controlling tumor development, showing that embryonic stem cell conditioned media are able to reduce metastatic phenotype of cancer cells. In this context, we have previously observed that human embryonic mesenchymal lung cells-conditioned medium (hEML-CM) are able to induce differentiation in tumor cells. Using this model, we aimed to identify relevant genes involved in the embryonic control of tumorogenesis in non-small cell lung cancer (NSCLC) and to evaluate their utility as prognostic biomarkers.
Methods
A549 cell line were cultured 48 hours in hEML-CM from human embryonic lungs of 10 weeks of development or control medium. Then, RNA was extracted and expression analysis was performed using Affymetrix HT Clariom™ S human microarray. After bioinformatic analysis, candidate genes were studied by qRT-PCR in a cohort of 91 early-stage NSCLC patients: mean age 69 years; 64.84% male; 48.35% stage I; 37.4% received adjuvant treatment; mean follow up 57 months; and 36 patients relapsed. The endpoints analyzed were disease free-survival (DFS) and overall survival (OS).
Results
A549 cells cultured with hEML-CM showed evidence of cell differentiation including morphological and molecular changes. Moreover, the metastatic potential of these cells was significantly reduced (lower proliferation and migration capacity). The analysis of the expression profile identified 7 genes previously linked to cancer, including DIO2 (p=0.003), which has been previously related to thyroid and brain development. In NSCLC patients DIO2 was upregulated in tumor tissue (p=0.002) and its expression was higher in smoking patients (p=0.035). Moreover, high levels of DIO2 were associated with shorter DFS (58.2 months vs. not reached; p=0.043) and shorter OS (76.3 months vs. not reached; p=0.024).
Conclusions
The study of embryonic genes involved in tumorogenesis allowed the identification of DIO2, a new promising prognostic biomarker for early-stage NSCLC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University of Barcelona.
Funding
Ministry of Economy, Industry, and Competition, “Agencia Estatal de Investigación” co-financed with the European Union FEDER funds SAF2017-88606-P (AEI/FEDER, UE).
Disclosure
All authors have declared no conflicts of interest.