Epigenetic markers-based breast cancer early detection method development

Abstract

Relevance: According to the International Agency for Research on Cancer (IARС), breast cancer ranks 1st-2nd among other cancers globally [1], including Kazakhstan [2]. In Kazakhstan, the annual growth in breast cancer incidence exceeds 26.6%. In 2018-2019, breast cancer
 was the 3rd most common cause of cancer death in Kazakhstan, accounting for 8.7-8.1 percent, respectively. Early detection of breast cancer
 remains an acute issue. In particular, early detection should be improved. Epigenetic studies of cancer patients confirm that epigenetic biomarkers could be used as early cancer diagnostic markers, including breast cancer.
 The study aimed to find specific diagnostic markers by methylation profiling of peripheral blood mononuclear cell (PBMC) DNA in breast
 cancer patients.
 Results: Plasma samples of the Kazakhstani population with breast cancer possessed mononuclear cell methylation markers in CpG islets associated with JAM3, C17orf64, MSC, and C7orf51 genes and the CpG islet associated with the intergenic region on chromosome 5, chr5:
 77,208,034-77,329,434, which were missing in healthy individuals. These biomarkers allow differentiating breast cancer from other cancers
 with a specificity of 0.91 and a sensitivity of 0.94 compared to methylation data from open DNA methylation databases (for Illumina 450K):
 TCGA, GSE40279, GSE61496, GSE76269 и GSE66836.
 Conclusion: Early breast cancer detection method using peripheral blood mononuclear cell DNA methylation profile, namely in CpG
 islets associated with JAM3, C17orf64, MSC, and C7orf51 genes and the CpG islet associated with the intergenic region on chromosome 5,
 chr5: 77,208,034-77,329,434 is enough specific and sensitive to use it in breast cancer screening.