Unknown,Transcriptomics,Genomics,Proteomics

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Expression of miRNAs in breast tumor from very youn women (<36) and women above 65 years old

ABSTRACT: miRNA expression from breast tumor tissue obtained from two groups of breast cancer (BC) patients: one group formed by women younger than 36 years and the other group by women older than 65 years. We selected breast tumor tissue samples from 21 women under 36 years old and 12 women above 65 years old, without BRCA mutation and without metastases. We selected a pool of samples in which all the subtypes were representated, in young patients as well as in older patients, to avoid expression biass. We add three samples from breast tissue of cancer-free women to minimize the age-related expression biass. Our aim was to compare miRNA expression between young women and older women, considering normal tissue as a reference.

ORGANISM(S): Homo sapiens

SUBMITTER: Gloria Ribas

PROVIDER: E-GEOD-48088 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Breast cancer in very young women (< 35 years BCVY) presents more aggressive and complex biological features than in their older counterparts. In this study we aimed to identify the key pathways that may cause cancer in this younger age group. EPIC and 450k Illumina methylation arrays were used to identify differences in DNA methylation in 74 breast cancer tumours, including 37 from very young women. Additionally, we analysed copy number variation (CNV) and DNAm age using methylation intensities from Illumina Infinium MethylationEPIC BeadChip. Although we are able to identify aberrant CNV patterns in breast cancer samples, they were not highly specific to BCVY. However, we identified 2 219 CpG sites that were differently methylated in BCVY vs. older women (false discovery rate < 0.05 beta-value difference ± 0.1), with the general hypomethylation profile affecting genes involved in neuronal-system pathways, cell communication, and extracellular matrix organisation, as confirmed by our experimental data. Additionally, a specific hypermethylation profile comprising 502 CpG sites located mainly in open-sea regions distinguished BCVY from older patients. Pathway enrichment analysis showed that regions implicated in the hypermethylation profile were involved in regulating genes related to Notch signalling pathways, the immune system, DNA repair, and vesicular trafficking. Moreover, BCVY presented age acceleration comparing with older women. The expression of genes regulated by differentially-methylated CpG sites was validated using both Cancer Genome Atlas genomic data and by qRT-PCR, the latter in an independent sample (n = 40). This validation highlighted that 186 genes were consistently deregulated, including consistent hypomethylation and higher expression of HOXD9, PCDH10, and HDAC5 genes when considering BCVY vs. BC. Thus, we propose HDAC5 hypomethylation as a possible early detection biomarker in BCVY, and moreover, HDAC5 inhibitors, such as LMK-235, may be useful in treating breast cancer tumours in young women

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Expression of miRNAs in breast tumor from very youn women (<36) and women above 65 years old

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