Identification of miRNA-Based Signature as a Novel Potential Prognostic Biomarker in Patients with Breast Cancer

Abstract

To identify the novel, noninvasive biomarkers to assess the outcome and prognosis of breast cancer (BC), patients with high sensitivity and specificity are greatly desired. Herein, the miRNA expression profile and matched clinical features of BC patients were extracted from The Cancer Genome Atlas (TCGA) database. The preliminary candidates were screened out by the univariate Cox regression test. Then, with the help of LASSO Cox regression analysis, the hsa-let-7b, hsa-mir-101-2, hsa-mir-135a-2, hsa-mir-22, hsa-mir-30a, hsa-mir-31, hsa-mir-3130-1, hsa-mir-320b-1, hsa-mir-3678, hsa-mir-4662a, hsa-mir-4772, hsa-mir-493, hsa-mir-556, hsa-mir-652, hsa-mir-6733, hsa-mir-874, and hsa-mir-9-3 were selected to construct the overall survival (OS) predicting signature, while the hsa-mir-130a, hsa-mir-204, hsa-mir-217, hsa-mir-223, hsa-mir-24-2, hsa-mir-29b-1, hsa-mir-363, hsa-mir-5001, hsa-mir-514a-1, hsa-mir-624, hsa-mir-639, hsa-mir-659, and hsa-mir-6892 were adopted to establish the recurrence-free survival (RFS) predicting signature. Referring to the median risk scores generated by the OS and RFS formulas, respectively, subgroup patients with high risk were strongly related to a poor OS and RFS revealed by Kaplan-Meier (K-M) plots. Meanwhile, receiver operating curve (ROC) analysis validated the accuracy and stability of these two signatures. When stratified by clinical features, such as tumor stage, age, and molecular subtypes, we found that the miRNA-based OS and RFS classifiers were still significant in predicting OS/RFS and showed the best predictive values than any other features. Besides, functional prediction analyses showed that these targeted genes of the enrolled miRNAs were enriched in cancer-associated pathways, such as MAPK/RTK, Ras, and PI3K-Akt signaling pathways. In summary, our observations demonstrate that the novel miRNA-based OS and RFS signatures are independent prognostic indicators for BC patients and worthy to be validated by further prospective studies.