Journal
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
Volume 202, Issue 3, Pages -Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.ajog.2009.11.037
Keywords
apoptotic signaling; cervical cancer; methylation; predictive marker; resistance to therapy
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Funding
- Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences
- Graduate School, Khon Kaen University, Khon Kaen, Thailand
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OBJECTIVE: We sought to investigate CpG-island methylation profiling of apoptotic genes apoptotic protease activating factor 1, caspase 8, death-associated protein kinase (DAPK), tumor necrosis factor receptor superfamily member 6 (FAS), Survivin, and tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and its role in resistance to therapy in cervical cancer (CXCA). STUDY DESIGN: Methylation status was performed in 85 CXCA patients comprising therapeutic nonresponses and responses using methylation-specific polymerase chain reaction. RESULTS: Methylation frequency of DAPK and FAS showed a statistically significant difference between therapeutic nonresponses and responses. Concurrent methylation of multiple apoptotic genes was a preferential event in CXCA. Moreover, concerted methylation of pair genes was observed in DAPK, FAS, and tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and found only in nonresponses. CONCLUSION: Aberrant methylation of apoptotic signaling genes results in acquired resistance to therapy. Detection of methylation in apoptotic signaling genes is potentially useful as a molecular predictive marker for strategic planning of treatment efficacy and evaluation of therapeutic outcome in CXCA, leading to an improvement of patients' survival.
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