Conjoint Analysis of DNA Methylation for Tumor Differentiation Using Cationic Conjugated Polymers

Molecular biomarkers, especially DNA methylation, are crucial discoveries for early detection of cancer. Compared with a single biomarker detection mode, using the conjoint detection mode can allow researchers to easily assess the association of the biomarkers with specific cancer. In this paper, we calculated the methylation status of RASSF1A, APC, CDKN2A/p16, and TMEFF2 genes using cationic conjugated polymers (CCPs)-based fluorescence resonance energy transfer (FRET) technique and then explored the connection between the overall DNA methylation status of the four genes and the clinical parameters of lung cancer patients. After analysis, no association was found between the methylation status of any single gene and the grade of tumor differentiation among 159 lung cancer samples analyzed. However, for conjoint analysis using the four genes, a statistically significant difference was reached between methylation status and the grade of tumor differentiation. The methylation levels in a panel of the four genes were correlated with sex, age, smoking pack-years, and lymphatic metastasis. Therefore, the conjoint analysis of DNA methylation in specific cancer-related genes could be a useful diagnostic tool for clinical implementation.