The landscape of PBMC methylome in canine mammary tumors reveals the epigenetic regulation of immune marker genes and its potential application in predicting tumor malignancy

Abstract

Background Genome-wide dysregulation of CpG methylation accompanies tumor progression and characteristic states of cancer cells, prompting a rationale for biomarker development. Understanding how the archetypic epige‑ netic modifcation determines systemic contributions of immune cell types is the key to further clinical benefts.

Results In this study, we characterized the diferential DNA methylome landscapes of peripheral blood mononu‑ clear cells (PBMCs) from 76 canines using methylated CpG-binding domain sequencing (MBD-seq). Through gene set enrichment analysis, we discovered that genes involved in the growth and diferentiation of T- and B-cells are highly methylated in tumor PBMCs. We also revealed the increased methylation at single CpG resolution and reversed expression in representative marker genes regulating immune cell proliferation (BACH2, SH2D1A, TXK, UHRF1). Furthermore, we utilized the PBMC methylome to efectively diferentiate between benign and malignant tumors and the presence of mammary gland tumors through a machine-learning approach.

Conclusions This research contributes to a better knowledge of the comprehensive epigenetic regulation of circulat‑ ing immune cells responding to tumors and suggests a new framework for identifying benign and malignant cancers using genome-wide methylome