A groundbreaking blood test has been developed by researchers at the Johns Hopkins Kimmel Cancer Center to detect early-stage cancers. This innovative approach, known as a liquid biopsy, measures the random variation in DNA methylation patterns rather than the absolute levels. The method, utilizing the Epigenetic Instability Index (EII), accurately distinguished patients with early-stage lung and breast cancers from healthy individuals. The research, supported by the National Institutes of Health, was published in Clinical Cancer Research and presented at the 2024 AACR meeting. The study's lead author, Hariharan Easwaran, highlights the significance of measuring DNA methylation variation, which outperforms measuring methylation alone. Thomas Pisanic, another key researcher, suggests that early-stage tumors with high methylation variation may be more aggressive. Liquid biopsies typically detect specific, absolute changes in methylation, but they often fail to perform well in diverse populations. To address this, Sara-Jayne Thursby analyzed cancer DNA methylation datasets to identify 269 specific genomic regions, known as CpG islands, which capture most DNA methylation variability across multiple cancer types. The team then trained a machine learning model to distinguish cancer signals from healthy signals, achieving remarkable accuracy across various cancer types. In lung adenocarcinoma, the EII demonstrated 81% sensitivity and 95% specificity in detecting stage 1A cancer. Early-stage breast cancer was also detected with approximately 68% sensitivity and 95% specificity. The tool showed promise in detecting signals from colon, brain, pancreatic, and prostate cancers as well. Easwaran and Pisanic believe that during the earliest stages of cancer development, methylation shifts, and these stochasticity metrics can help identify and intercept early-stage carcinogenesis. The team is now expanding and improving the method to develop the EII into a diagnostic tool, aiming to complement existing screening tools like DELFI and other DNA mutation-based assays. While further validation is needed, the EII has the potential to be a valuable 'secondary triaging measure' in clinical settings.
