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eISSN: 1643-3750

Identification of a DNA Methylation-Based Prognostic Signature for Patients with Triple-Negative Breast Cancer

Yinqi Gao, Xuelong Wang, Shihui Li, Zhiqiang Zhang, Xuefei Li, Fangcai Lin

Department of Breast Surgery, Capital Medical University Electric Power Teaching Hospital, Beijing, China (mainland)

Med Sci Monit 2021; 27:e930025

DOI: 10.12659/MSM.930025

Available online: 2021-03-01

Published: 2021-05-18


#930025

BACKGROUND: Aberrant DNA methylation is an important biological regulatory mechanism in malignant tumors. However, it remains underutilized for establishing prognostic models for triple-negative breast cancer (TNBC).
MATERIAL AND METHODS: Methylation data and expression data downloaded from The Cancer Genome Atlas (TCGA) were used to identify differentially methylated sites (DMSs). The prognosis-related DMSs were selected by univariate Cox regression analysis. Functional enrichment was analyzed using DAVID. A protein-protein interaction (PPI) network was constructed using STRING. Finally, a methylation-based prognostic signature was constructed using LASSO method and further validated in 2 validation cohorts.
RESULTS: Firstly, we identified 743 DMSs corresponding to 332 genes, including 357 hypermethylated sites and 386 hypomethylated sites. Furthermore, we selected 103 prognosis-related DMSs by univariate Cox regression. Using a LASSO algorithm, we established a 5-DMSs prognostic signature in TCGA-TNBC cohort, which could classify TNBC patients with significant survival difference (log-rank p=4.97E-03). Patients in the high-risk group had shorter overall survival than patients in the low-risk group. The excellent performance was validated in GSE78754 (HR=2.42, 95%CI: 1.27-4.59, log-rank P=0.0055). Moreover, for disease-free survival, the prognostic performance was verified in GSE141441 (HR=2.09, 95%CI: 1.28-3.44, log-rank P=0.0027). Multivariate Cox regression analysis indicated that the 5-DMSs signature could serve as an independent risk factor.
CONCLUSIONS: We constructed a 5-DMSs signature with excellent performance for the prediction of disease-free survival and overall survival, providing a guide for clinicians in directing personalized therapeutic regimen selection of TNBC patients.

Keywords: DNA Methylation, Prognosis, Triple Negative Breast Neoplasms



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