Background: MicroRNAs (miRNAs) play a critical role in the carcinogenesis and progression of breast cancer. MiRNA-205 has tumor suppressive properties, whereas miRNA-18a has both oncogenic and tumor suppressive roles. MiRNA-744's role in breast cancer is unknown but is tumor-suppressive in vitro. We hypothesize that high expression of all three miRNAs is associated with a better survival based on their known functions in breast cancer.
Methods: All data was obtained from the Cancer Genome Atlas (TCGA). Expression patterns of miRNA-18a, miRNA-205, and miRNA-744 were retrieved from the Genomic Data Commons (GDC) data portal for analyses. After miRNA-specific thresholds were derived and used to group the patients into a high- or low-expression group, survival data was calculated by using the Cox proportional hazard model. Further subanalyses separating the patients based on receptor status and AJCC 7th edition TNM staging were similarly compared.
Results: In total, 1,052 of 1,097 samples logged in TCGA had clinical data and miRNA-sequence datasets on the miRNAs of interest. High expression of miRNA-18a (p = 0.079), miRNA-205 (p = 0.034), and miRNA-744 (p = 0.0135) was associated with better survival. On subanalysis, estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, and lymph node-negative disease had a statistically significant survival advantage with miRNA-18a, miRNA-205, and miRNA-744 high expression.
Conclusions: By utilizing a big dataset (TCGA) with sufficient statistical power, we found that high expression of miRNA-18a, miRNA-205, and miRNA-744 in the breast tumor samples were all associated with better overall survival in ER/PR-positive, lymph node-negative disease supporting their role as a tumor suppressor in breast cancer.