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


METHODS
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.


CONCLUSIONS
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.
Chaopatchayakul
Patimaporn
P
Department of Clinical Chemistry, the Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Jearanaikoon
Patcharee
P
Yuenyao
Pissamai
P
Limpaiboon
Temduang
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D053181:Caspase 8 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D064550:Death-Associated Protein Kinases; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D000077022:Survivin; D017211:Treatment Failure; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D019014:fas Receptor / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; C107489:BIRC5 protein, human; D005819:Genetic Markers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D000077022:Survivin; C105190:TNFRSF10A protein, human; D019014:fas Receptor; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C505530:CASP8 protein, human; D053181:Caspase 8