Circulating microRNAs miR-331 and miR-195 differentiate local luminal a from metastatic breast cancer.
BACKGROUND
Breast cancer is the leading cause of cancer related death in women, with metastasis the principle cause of mortality. New non-invasive prognostic markers are needed for the early detection of metastasis, facilitating treatment decision optimisation. MicroRNA (miRNA) are small, non-coding RNAs regulating gene expression and involved in many cellular processes, including metastasis. As biomarkers, circulating miRNAs (in blood) hold great promise for informing diagnosis or monitoring treatment responses.


METHODS
Plasma extracted RNA from age matched local Luminal A (n = 4) or metastatic disease (n = 4) were profiled using Next Generation Sequencing. Selected differentially expressed miRNA were validated on a whole blood extracted miRNA cohort [distant metastatic disease (n = 22), local disease (n = 31), healthy controls (n = 21)]. Area Under the Curve (AUC) in Receiver Operating Characteristic (ROC) analyses was performed.


RESULTS
Of 4 miRNA targets tested (miR-181a, miR-329, miR-331, miR-195), mir-331 was significantly over-expressed in patients with metastatic disease, compared to patients with local disease (p < 0.001) or healthy controls (p < 0.001). miR-195 was significantly under-expressed in patients with metastatic disease, compared to patients with local disease (p < 0.001) or healthy controls (p = 0.043). In combination, miR-331 and miR-195 produced an AUC of 0.902, distinguishing metastatic from local breast cancer.


CONCLUSIONS
We identified and validated two circulating miRNAs differentiating local Luminal A breast cancers from metastatic breast cancers. Further investigation will reveal the molecular role of these miRNAs in metastasis, and determine if they are subtype specific. This work demonstrates the ability of circulating miRNA to identify metastatic disease, and potentially inform diagnosis or treatment effectiveness.
['McAnena|Peter|P|http://orcid.org/0000-0003-1179-7150', 'Tanriverdi|Kahraman|K|', 'Curran|Catherine|C|', 'Gilligan|K|K|', 'Freedman|Jane E|JE|', 'Brown|James A L|JAL|http://orcid.org/0000-0002-3155-0334', 'Kerin|Michael J|MJ|']
D000328:Adult D000368:Aged D014408:Biomarkers, Tumor D001943:Breast Neoplasms D003937:Diagnosis, Differential D005260:Female D015972:Gene Expression Regulation, Neoplastic D059014:High-Throughput Nucleotide Sequencing D006801:Humans D035683:MicroRNAs D008875:Middle Aged D009362:Neoplasm Metastasis D011446:Prospective Studies D012372:ROC Curve D017423:Sequence Analysis, RNA D015854:Up-Regulation
miR-331 miR-195 Breast Cancer Metastasis miRNA Biomarker