DNA methylation biomarker analysis from low-survival-rate cancers based on genetic functional approaches

Identifying cancer biomarkers through DNA methylation analysis is an efficient approach toward the detection of aberrant changes in epigenetic regulation associated with early-stage cancer types. Among all cancer types, cancers with relatively low five-year survival rates and high incidence rates were pancreatic (10%), esophageal (20%), liver (20%), lung (21%), and brain (27%) cancers. This study integrated genome-wide DNA methylation profiles and comorbidity patterns to identify the common biomarkers with multi-functional analytics across the aforementioned five cancer types. In addition, gene ontology was used to categorize the biomarkers into several functional groups and establish the relationships between gene functions and cancers. ALX3, HOXD8, IRX1, HOXA9, HRH1, PTPRN2, TRIM58, and NPTX2 were identified as important methylation biomarkers for the five cancers characterized by low five-year survival rates. To extend the applicability of these biomarkers, their annotated genetic functions were explored through GO and KEGG pathway analyses. The combination of ALX3, NPTX2, and TRIM58 was selected from distinct functional groups. An accuracy prediction of 93.3% could be achieved by validating the ten most common cancers, including the initial five low-survival-rate cancer types.