Aberrant DNA methylation of apoptotic signaling genes in patients responsive and nonresponsive to therapy for cervical carcinoma

作者：Chaopatchayakul Patima****; Jearanaikoon Patcharee; Yuenyao Pissamai; Limpaiboon Temduang^*

来源：American Journal of Obstetrics and Gynecology, 2010, 202(3): 281.e1.

DOI：10.1016/j.ajog.2009.11.037

• apoptotic signaling
• cervical cancer
• methylation
• predictive marker
• resistance to therapy

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.

• 出版日期2010-3