Several prognostic factors are currently used to stratify breast cancer patients based on the risk of disease progression. However, even patients classified as at low risk can progress and die for the disease. MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types including breast cancer.
We evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n=150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ≥7.0 were analyzed. The relative expression of miR-10b in tumor as compared to its normal counterpart (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of patients with synchronous metastases (n=11, Median 0.25; IQR 0.11-1.02) as compared with patients without metastases (n=90, Median 0.09; IQR 0.04-0.29) (p=0.028). In the subgroup of patients without synchronous metastases (n=90), higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable (HR 4.35, p=0.021 and HR 6.02, p=0.015 respectively) and multivariable (HR 13.37, p<0.001, and HR 15.39, p=0.003 respectively) Cox regression models. The addition of miR-10b RERs to the Nottingham Prognostic Index (NPI) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months. Survival C-indices significantly increased from 0.849 to 0.889 (p=0.009) for OS and from 0.735 to 0.767 (p=0.050) for DFS.
Our results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients.
Citation Format: Paola Parrella, Raffaela Barbano, Barbara Pasculli, Andrea Fontana, Massimiliano Copetti, Vanna Maria Valori, Maria Luana Poeta, Giuseppe Perrone, Michelina Coco, Teresa Balsamo, Fabio Pellegrini, Andrea Onetti Muda, Evaristo Maiello, Roberto Murgo, Vito Michele Fazio. Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1477. doi:10.1158/1538-7445.AM2014-1477