26P - Global transcriptome deregulation of Breast Cancer in Very Young Women samples

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Basic Science
Cancer in Young Adults
Breast Cancer
Presenter Victoria Vidal Tomas
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors V. Vidal Tomas1, S. Oltra Sanchis1, M. Martinez2, E. Alonso2, O. Burgues3, A. Lluch2, M.P. Chilet1, G. Ribas1
  • 1Medical Oncology, Biomedical Research institute INCLIVA - University of Valencia, 46010 - Valencia/ES
  • 2Medical Oncology  , Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 3Pathological Anatomy, Hospital Clínico Universitario de Valencia, 46010 - Valencia/ES

Abstract

Background

Breast cancer in young women (under 35 years) (BCVY) often presents distinct clinic-pathological features: more aggressive phenotype and worse prognosis than older women. Genomic and molecular alterations play a significant role in breast cancer biology. Due to the low incidence of BCVY (2-5%) these women are underrepresented in most molecular studies. This work presents a comprehensive study of the transcriptome in BCVY, focusing in the search of gene expression biomarkers characteristic of this group of patients.

Methods

We analysed the transcriptome by Clariom™ D (Affymetrix) from 31 BCVY and 11 samples from women >45 years old. Global gene expression was filtered and normalized by RMA method. After initial pre-processing we analysed expression in 3,639 mRNAs, 66,457 lncRNA and 3,271 pre-miRNA and differences were assessed using t-test. We performed a meta-analysis with gene expression data from The Cancer Genome Atlas (TCGA) for validation of results. Pathway enrichment analysis was performed by Enrichr.

Results

showed a specific transcriptomic landscape in BCVY. Clariom D study revealed 134 significant mRNA with p-value< 0.05 that pointed out towards pathways related with olfactory receptors, GPCR signalling, tight junction and cell-cell communication. After meta-analysis with TCGA gene expression data and own data, 43 genes were statistically significant and 15 of those withstood FDR correction (FDR< 0.05). Among those we found PIK3CB, HOXD10, ZNF654, TMEM204, IRX5, PF4, MAGEA2 and TSR2 deregulated in BCVY compared with older women. Pathway enrichment analyses and GO search highlight pathways related to cell-cell communication, cancer processes, chemokine and PI3K signalling pathways, cell differentiation, extracellular matrix, vesicular trafficking, neuronal processes among others.

Conclusions

We find the presence of a distinctive transcriptomic profile of the BCVY samples. Our study points to deregulation of pathways related to cell migration, proliferation and differentiation that promote cancer development and progression. Genes obtained in meta-analyse might be potential target genes for further studies in BCVY which could help to clarify the biological background for the development of the disease in this group of age.

Clinical trial identification

Legal entity responsible for the study

INCLIVA Instituto de investigación

Funding

None

Disclosure

S. Sanchis: Funded on a FPU predoctoral Fellowship (FPU13/04976) from MINECO, Spanish Government. G. Ribas: Funded on a Miquel Servet II contract (CPII14-00013) from CarlosIII Health Institute. M.P. Chilet: Funded by private Patients Fundation LeCado. CIBERONC is an initiative of the Carlos III Health Institute. All other authors have declared no conflicts of interest.