Evaluation of Pan-Cancer Immune Heterogeneity Based on DNA Methylation

Abstract: Background/Objectives: The heterogeneity of the tumor immune microenvironment is a key determinant of tumor oncogenesis. This study aims to evaluate the composition of seven immune cells across 5323 samples from 14 cancers using DNA methylation data. Methods: A deconvolution algorithm was proposed to estimate the composition of seven immune cells using 1256 immune cell population-specific methylation genes. Based on the immune infiltration features of seven immune cell fractions, 42 subtypes of 14 tumors (2–5 subtypes per tumor) were identified. Results: Significant differences in immune cells between subtypes were revealed for each cancer. The study found that the methylation values of the selected specific sites correlated with gene expression in most tumor subtypes. Immune infiltration results were integrated with phenotypic data, including survival data and tumor stages, revealing significant correlations between immune infiltration and phenotypes in some tumors. Subtypes with high proportions of CD4+ T cells, CD8+ T cells, CD56+ NK cells, CD19+ B cells, CD14+ monocytes, neutrophils, and eosinophils were identified, with subtype counts of 9, 24, 22, 13, 19, 9, and 11, respectively. Additionally, 2412 differentially expressed genes between these subtypes and normal tissues were identified. Pathway enrichment analysis revealed that these genes were mainly enriched in pathways related to drug response and chemical carcinogens. Differences in ESTIMATE scores for subtypes of seven tumors and TIDE scores for eight tumors were also observed. Conclusions: This study demonstrates the intra-tumor and inter-tumor immune heterogeneity of pan-cancer through DNA methylation analysis, providing assistance for tumor diagnosis.