Integrative Analysis of Gene Expression and DNA Methylation Depicting the Impact of Obesity on Breast Cancer

Obesity has been reported to be a risk factor for breast cancer, but how obesity affects breast cancer (BC) remains unclear. Although body mass index (BMI) is the most commonly used reference for obesity, it is insufficient to evaluate the obesity-related pathophysiological changes in breast tissue. The purpose of this study is to establish a DNA-methylation-based biomarker for BMI (DM-BMI) and explore the connection between obesity and BC. Using DNA methylation data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we developed DM-BMI to evaluate the degree of obesity in breast tissues. In tissues from non-BC and BC population, the DM-BMI model exhibited high accuracy in BMI prediction. In BC tissues, DM-BMI correlated with increased adipose tissue content and BC tissues with increased DM-BMI exhibited higher expression of pro-inflammatory adipokines. Next, we identified the gene expression profile relating to DM-BMI. Using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we observed that the DM-BMI-related genes were mostly involved in the process of cancer immunity. DM-BMI is positively correlated with T cell infiltration in BC tissues. Furthermore, we observed that DM-BMI was positively correlated with immune checkpoint inhibitors (ICI) response markers in BC. Collectively, we developed a new biomarker for obesity and discovered that BC tissues from obese individuals exhibit an increased degree of immune cell infiltration, indicating that obese BC patients might be the potential beneficiaries for ICI treatment.