A prognostic signature of six necroptosis-related miRNAs for predicting the overall survival of breast cancer patients

Abstract

Breast cancer (BRCA) is the most frequent malignant disease and cause of death in females. Recent studies have uncovered the crucial roles of necroptosis-related miRNAs in diverse cancers, including BRCA. However, the significance of necroptosis-related miRNA in predicting the prognosis of BRCA remains largely undefined. This study aimed at constructing a miRNA risk signature related to necroptosis and a nomogram for estimating the prognosis of BRCA. The miRNA expression data and related clinical information were downloaded from the BRCA cohort (containing tissue samples from BRCA patients and normal para-cancer patients) of The Cancer Genome Atlas (TCGA) database. We analyzed the miRNA expression profile and screened the differentially expressed necroptosis-related miRNAs between BRCA and non-tumor samples. Then, a risk signature for BRCA patients was developed based on prognostic necroptosis-related miRNAs. The prognostic value of the risk signature was determined by Cox regression analysis. We also constructed a prognostic nomogram based on risk signature and clinicopathological characteristics, and evaluated its clinical potential using a calibration chart. Lastly, to identify potential therapeutic target for BRCA. Six necroptosis-related miRNAs (miR-141-3p, miR-148a-3p, miR-200a-5p, miR-223-3p, miR-425-5p, miR-7-5p) were differentially expressed between normal and BRCA tissues, including five up-regulated miRNAs and one down-regulated miRNA. They were used to construct the risk signature. Receiver Operating Characteristic (ROC) curve analysis indicated that the risk signature had good sensitivity and specificity (2-year area under curve (AUC): 0.627; 3-year AUC: 0.647) and was an independent prognostic factor (univariate Cox regression: hazard ratio (HR) = 1.8066, 95% confidence interval (CI) (1.2867–2.5365), p < 0.05; multivariate Cox regression: HR = 1.5246, 95% CI (1.0830–2.1462), p < 0.05). Calibration chart showed that the nomogram had good accuracy for predicting the prognosis of BRCA patients. We also identified miR-223a-3p as a potential therapeutic target for BRCA. This study identified 6 promising necroptosis-related miRNAs, which were used to construct a signature model to predict BRCA patients’ prognosis. Further, a nomogram based on risk signatures and clinicopathological characteristics was constructed and showed promising potential as an effective and individualized diagnostic tool.