TY - JOUR
T1 - Prognostic role of elevated mir-24-3p in breast cancer and its association with the metastatic process
AU - Khodadadi-Jamayran, Alireza
AU - Akgol-Oksuz, Betul
AU - Afanasyeva, Yelena
AU - Heguy, Adriana
AU - Thompson, Marae
AU - Ray, Karina
AU - Giro-Perafita, Ariadna
AU - Sánchez, Irma
AU - Wu, Xifeng
AU - Tripathy, Debu
AU - Zeleniuch-Jacquotte, Anne
AU - Tsirigos, Aristotelis
AU - Esteva, Francisco J.
N1 - Publisher Copyright:
© Khodadadi-Jamayran et al.
PY - 2018
Y1 - 2018
N2 - MicroRNAs have been shown to play important roles in breast cancer progression and can serve as biomarkers. To assess the prognostic role of a panel of miRNAs in breast cancer, we collected plasma prospectively at the time of initial diagnosis from 1,780 patients with stage I-III breast cancer prior to definitive treatment. We identified plasma from 115 patients who subsequently developed distant metastases and 115 patients without metastatic disease. Both groups were matched by: age at blood collection, year of blood collection, breast cancer subtype, and stage. The median follow up was 3.4 years (range, 1-9 years). We extracted RNA from plasma and analyzed the expression of 800 miRNAs using Nanostring technology. We then assessed the expression of miRNAs in primary and metastatic breast cancer samples from The Cancer Genome Atlas (TCGA). We found that, miR-24-3p was upregulated in patients with metastases, both in plasma and in breast cancer tissues. Patients whose primary tumors expressed high levels of miR-24-3p had a significantly lower survival rate compared to patients with low mir-24-3p levels in the TCGA cohort (n=1,024). RNA-Seq data of the samples with the highest miR-24-3p expression versus those with the lowest miR-24-3p in the TCGA cohort identified a specific gene expression signature for those tumors with high miR-24-3p. Possible target genes for miR-24- 3p were predicted based on gene expression and binding site, and their effects on cancer pathways were evaluated. Cancer, breast cancer and proteoglycans were the top three pathways affected by miR-24-3p overexpression.
AB - MicroRNAs have been shown to play important roles in breast cancer progression and can serve as biomarkers. To assess the prognostic role of a panel of miRNAs in breast cancer, we collected plasma prospectively at the time of initial diagnosis from 1,780 patients with stage I-III breast cancer prior to definitive treatment. We identified plasma from 115 patients who subsequently developed distant metastases and 115 patients without metastatic disease. Both groups were matched by: age at blood collection, year of blood collection, breast cancer subtype, and stage. The median follow up was 3.4 years (range, 1-9 years). We extracted RNA from plasma and analyzed the expression of 800 miRNAs using Nanostring technology. We then assessed the expression of miRNAs in primary and metastatic breast cancer samples from The Cancer Genome Atlas (TCGA). We found that, miR-24-3p was upregulated in patients with metastases, both in plasma and in breast cancer tissues. Patients whose primary tumors expressed high levels of miR-24-3p had a significantly lower survival rate compared to patients with low mir-24-3p levels in the TCGA cohort (n=1,024). RNA-Seq data of the samples with the highest miR-24-3p expression versus those with the lowest miR-24-3p in the TCGA cohort identified a specific gene expression signature for those tumors with high miR-24-3p. Possible target genes for miR-24- 3p were predicted based on gene expression and binding site, and their effects on cancer pathways were evaluated. Cancer, breast cancer and proteoglycans were the top three pathways affected by miR-24-3p overexpression.
KW - Breast cancer
KW - Gene expression profiling
UR - http://www.scopus.com/inward/record.url?scp=85042566310&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042566310&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.24403
DO - 10.18632/oncotarget.24403
M3 - Article
C2 - 29560116
AN - SCOPUS:85042566310
SN - 1949-2553
VL - 9
SP - 12868
EP - 12878
JO - Oncotarget
JF - Oncotarget
IS - 16
ER -