High uPAR and Low miR-221 Expression Predict Poor Disease-Free Survival in Triple-Negative Breast Cancer

Area of Science:

• Oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and limited therapeutic strategies.
• The urokinase plasminogen activator receptor (uPAR) is implicated in tumor progression, and its regulation by microRNAs, such as miR-221, is under investigation.
• Identifying reliable prognostic markers is crucial for managing TNBC patients.

Purpose of the Study:

• To investigate the prognostic significance of urokinase plasminogen activator receptor (uPAR) mRNA and miR-221 expression in triple-negative breast cancer (TNBC).
• To determine the potential of uPAR and miR-221 as independent or combined biomarkers for predicting disease-free survival (DFS) in TNBC patients.

Main Methods:

• Quantitative real-time PCR was employed to measure uPAR mRNA and miR-221 levels in tumor tissues from 101 TNBC patients.
• Univariate and multivariable Cox regression analyses were used to assess associations with clinicopathological parameters and DFS.
• In silico analyses of public datasets were conducted for validation and to predict additional targets of miR-221.

Main Results:

• High uPAR mRNA expression was significantly correlated with shorter DFS, whereas high miR-221 expression was associated with improved DFS.
• No direct inverse correlation was found between uPAR and miR-221, suggesting independent roles.
• A combined analysis revealed that high uPAR and low miR-221 expression identified patients with the poorest DFS, a finding supported by in silico data.

Conclusions:

• uPAR mRNA and miR-221 function as independent prognostic markers in triple-negative breast cancer.
• The combined assessment of uPAR and miR-221 expression enhances prognostic prediction for DFS in TNBC.
• These findings highlight uPAR and miR-221 as potential biomarkers and therapeutic targets for TNBC.