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.
Highlights
A sum of 268,600 new invasive breast cancer (BC) cases are estimated in the United States in 2019, with an approximate 41,760 BC-related deaths [1]; the average 5-year survival rate for women with invasive breast cancer is 90%, and the average 5-year overall survival (OS) of BC patients are different from 99% to 27% due to the different stages of pathological development
We investigated and confirmed that the miRNA-based OS/recurrence-free survival (RFS) classifiers might potentially facilitate predicting the prognosis and clinical outcome of BC patients
Our results demonstrated that the OS model could distinguish the patients of BC with poor and good overall survival according to their risk score, and the 13-miRNA-based RFS classifier was robust to predict the outcomes of patients with BC
Summary
A sum of 268,600 new invasive breast cancer (BC) cases are estimated in the United States in 2019, with an approximate 41,760 BC-related deaths [1]; the average 5-year survival rate for women with invasive breast cancer is 90%, and the average 5-year overall survival (OS) of BC patients are different from 99% to 27% due to the different stages of pathological development. The OncotypeDX model, a 21-gene signature, is regarded as one of the best-validated breast cancer multigene signatures, suggesting a stratification of the fiveyear or ten-year risk of distant relapse [3]. Disease Markers status and predict the prognosis of cancer patients. As the single-strand RNA is small, they have recently emerged as pivotal gene expression regulatory molecules in the multicellular organism [4]. Accumulating evidence has shown that expression of the miRNA and its target genes is influenced at numerous levels, including epigenetic effects, promoter regulation, RNA processing and stability, and translation, having functional effects on cell proliferation, apoptosis, metastasis, and sensitivity to chemotherapy and radiotherapy in breast cancer [5]. Screened by 1000 BC samples, we retrieved to make an understanding of the relationship of miRNA expression level with the prognosis and outcome of BC patients
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