Communications medicine · 2024
Clinical validation of peripheral blood mononuclear cell DNA methylation markers for accurate early detection of hepatocellular carcinoma in Asian patients.
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Cheishvili David, Wong Chifat, Karim Mohammad Mahbubul, Golam Kibria Mohammad, Jahan Nusrat, Chandra Das Pappu, Khair Yousuf Abul, Islam Atikul, Chandra Das Dulal, Noor-E-Alam Sheikh Mohammad, Alam Sarwar, Rahman Mustafizur, Khan Wasif A, Al-Mahtab Mamun, Szyf Moshe
Аннотация
BACKGROUND: Hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths globally, poses significant challenges in early detection. Improved diagnostic accuracy can drastically influence patient outcomes, emphasizing the need for innovative, non-invasive biomarkers.
METHODS: This study utilized a cohort of 402 participants, including healthy controls, chronic hepatitis patients, and HCC patients from Bangladesh, to evaluate DNA methylation signatures in peripheral blood mononuclear cells (PBMC). We performed targeted next-generation sequencing on selected genes previously identified to assess their methylation dynamics. The development of M8 and M4 scores was based on these dynamics, using Receiver Operating Characteristic (ROC) analysis to determine their effectiveness in detecting early-stage HCC alongside existing markers such as epiLiver and alpha-fetoprotein (AFP).
RESULTS: Integration of M8 and M4 scores with epiLiver and AFP significantly enhances diagnostic sensitivity for early-stage HCC. The M4+epiLiver score achieves a sensitivity of 79.4% in Stage A HCC, while combining M4 with AFP increases sensitivity to 88.2-95.7% across all stages, indicating a superior diagnostic performance compared to each marker used alone.
CONCLUSIONS: Our study confirms that combining gene methylation profiles with established diagnostic markers substantially improves the sensitivity of detecting early-stage HCC. This integrated diagnostic approach holds promise for advancing non-invasive cancer diagnostics, potentially leading to earlier treatment interventions and improved survival rates for high-risk patients.
METHODS: This study utilized a cohort of 402 participants, including healthy controls, chronic hepatitis patients, and HCC patients from Bangladesh, to evaluate DNA methylation signatures in peripheral blood mononuclear cells (PBMC). We performed targeted next-generation sequencing on selected genes previously identified to assess their methylation dynamics. The development of M8 and M4 scores was based on these dynamics, using Receiver Operating Characteristic (ROC) analysis to determine their effectiveness in detecting early-stage HCC alongside existing markers such as epiLiver and alpha-fetoprotein (AFP).
RESULTS: Integration of M8 and M4 scores with epiLiver and AFP significantly enhances diagnostic sensitivity for early-stage HCC. The M4+epiLiver score achieves a sensitivity of 79.4% in Stage A HCC, while combining M4 with AFP increases sensitivity to 88.2-95.7% across all stages, indicating a superior diagnostic performance compared to each marker used alone.
CONCLUSIONS: Our study confirms that combining gene methylation profiles with established diagnostic markers substantially improves the sensitivity of detecting early-stage HCC. This integrated diagnostic approach holds promise for advancing non-invasive cancer diagnostics, potentially leading to earlier treatment interventions and improved survival rates for high-risk patients.