Construction of a MicroRNA-Based Nomogram for Prediction of Lung Metastasis in Breast Cancer Patients

Abstract

The lung is one of the most common sites of distant metastasis in breast cancer (BC). Identifying ideal biomarkers to construct a more accurate prediction model than conventional clinical parameters is crucial. MicroRNAs (miRNAs) data and clinicopathological data were acquired from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database. miR-663, miR-210, miR-17, miR-301a, miR-135b, miR-451, miR-30a, and miR-199a-5p were screened to be highly relevant to lung metastasis (LM) of BC patients. The miRNA-based risk score was developed based on the logistic coefficient of the individual miRNA. Univariate and multivariate logistic regression selected tumor node metastasis (TNM) stage, age at diagnosis, and miRNA-risk score as independent predictive parameters, which were used to construct a nomogram. The Cancer Genome Atlas (TCGA) database was used to validate the signature and nomogram. The predictive performance of the nomogram was compared to that of the TNM stage. The area under the receiver operating characteristics curve (AUC) of the nomogram was higher than that of the TNM stage in all three cohorts (training cohort: 0.774 vs. 0.727; internal validation cohort: 0.763 vs. 0.583; external validation cohort: 0.925 vs. 0.840). The calibration plot of the nomogram showed good agreement between predicted and observed outcomes. The net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision-curve analysis (DCA) of the nomogram showed that its performances were better than that of the TNM classification system. Functional enrichment analyses suggested several terms with a specific focus on LM. Subgroup analysis showed that miR-30a, miR-135b, and miR-17 have unique roles in lung metastasis of BC. Pan-cancer analysis indicated the significant importance of eight predictive miRNAs in lung metastasis. This study is the first to establish and validate a comprehensive lung metastasis predictive nomogram based on the METABRIC and TCGA databases, which provides a reliable assessment tool for clinicians and aids in appropriate treatment selection.