MiRNA expression deregulation correlates with the Oncotype DX^® DCIS score

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Current clinical criteria inadequately predict invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) recurrence.
• The Oncotype DX® DCIS assay predicts recurrence risk but may benefit from complementary biomarkers.
• MicroRNA (miRNA) deregulation is implicated in IBC development, yet its role in DCIS requires further investigation.

Purpose of the Study:

• To investigate the correlation between specific miRNA expression deregulation and Oncotype DX® DCIS scores.
• To identify miRNAs that can enhance the predictive accuracy of the Oncotype DX® DCIS assay.
• To explore the potential of miRNA expression profiling in assessing DCIS prognosis.

Main Methods:

• Utilized formalin-fixed, paraffin-embedded (FFPE) DCIS specimens from 41 patients.
• Stratified DCIS lesions into low, intermediate, and high-risk groups using the Oncotype DX® DCIS assay.
• Performed next-generation small-RNA sequencing and RT-qPCR validation to analyze miRNA expression and correlate it with Oncotype scores and patient age.

Main Results:

• A significant correlation was found between the expression deregulation of 17 miRNAs and Oncotype scores.
• Expression deregulation of 9 miRNAs correlated with patient age.
• A panel of 5 miRNAs (miR-190b, miR-135a, miR-205, miR-30c, miR-744) showed decreased expression in intermediate/high-risk groups and formed a composite score significantly associated with Oncotype DX® DCIS scores.

Conclusions:

• Identified a specific subset of 5 miRNAs capable of discriminating between Oncotype DX® DCIS score subgroups.
• MiRNA expression analysis demonstrates potential to augment the predictive and prognostic evaluation of DCIS.
• These findings suggest that miRNA profiling could offer added value in managing DCIS patients.