Diagnostic classification of cancers using DNA methylation of paracancerous tissues

Abstract The potential role of DNA methylation from paracancerous tissues in cancer diagnosis has not been explored until now. In this study, we built classification models using well-known machine learning models based on DNA methylation profiles of paracancerous tissues. We evaluated our methods on nine cancer datasets collected from The Cancer Genome Atlas (TCGA) and utilized fivefold cross-validation to assess the performance of models. Additionally, we performed gene ontology (GO) enrichment analysis on the basis of the significant CpG sites selected by feature importance scores of XGBoost model, aiming to identify biological pathways involved in cancer progression. We also exploited the XGBoost algorithm to classify cancer types using DNA methylation profiles of paracancerous tissues in external validation datasets. Comparative experiments suggested that XGBoost achieved better predictive performance than the other four machine learning methods in predicting cancer stage. GO enrichment analysis revealed key pathways involved, highlighting the importance of paracancerous tissues in cancer progression. Furthermore, XGBoost model can accurately classify nine different cancers from TCGA, and the feature sets selected by XGBoost can also effectively predict seven cancer types on independent GEO datasets. This study provided new insights into cancer diagnosis from an epigenetic perspective and may facilitate the development of personalized diagnosis and treatment strategies.