ORIGINAL RESEARCH

Identification of prognostically significant DNA methylation signatures in patients with various breast cancer types

Kalinkin AI1, Sigin VO1, Nemtsova MV1,2, Strelnikov VV1,3
About authors

1 Research Centre for Medical Genetics, Moscow, Russia

2 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

3 Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Alexey I. Kalinkin
Moskvorechye, 1, Moscow, 115522; ur.xednay@2akiexela

About paper

Funding: the study was supported by the Ministry of Science and Higher Education of the Russian Federation within the framework of the Federal Scientific and Technical Program for the Development of Genetic Technologies in 2019–2027 (agreement № 075-15-2021-1073).

Author contribution: Kalinkin AI — study design, data acquisition, analysis and interpretation, manuscript writing; Sigin VO — manuscript writing; Nemtsova MV — study concept and design; Strelnikov VV — study concept and design, scientific editing.

Received: 2022-10-18 Accepted: 2022-11-11 Published online: 2022-11-25
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Breast cancer (BC) is the most frequently diagnosed cancer and one of the major causes of female mortality. The development of prognostic models based on multiomics data is the main goal of precision oncology. Aberrant DNA methylation in BC is a diagnostic marker of carcinogenesis. Despite the existing factors of BC prognosis, introduction of methylation markers would make it possible to obtain more accurate prognostic scores. The study was aimed to assess DNA methylation signatures in various BC subtypes for clinical endpoints and patients' clinicopathological characteristics. The data on methylation of CpG dinucleotides (probes) and clinical characteristics of BC samples were obtained from The Cancer Genome Atlas Breast Cancer database. CpG dinucleotides associated with the selected endpoints were chosen by univariate Cox regression method. The LASSO method was used to search for stable probes, while further signature construction and testing of the clinical characteristics independence were performed using multivariate Cox regression. The dignostic and prognostic potential of the signatures was assessed using ROC analysis and Kaplan–Meier curves. It has been shown that the signatures of selected probes have a significant diagnostic (AUC 0.76–1) and prognostic (p < 0.05) potential. This approach has made it possible to identify 47 genes associated with good and poor prognosis, among these five genes have been described earlier. If the genome-wide DNA analysis results are available, the research approach applied can be used to study molecular pathogenesis of BC and other disorders.

Keywords: breast cancer, DNA methylation, molecular subtypes, survival analysis, prognostic markers

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