Epigenetic silencing of cyclooxygenase-2 affects clinical outcome in gastric cancer
Inventors
Hoon, Dave S. B. • DE MAAT, Michiel
Assignees
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Publication Number
US-7851161-B2
Publication Date
2010-12-14
Expiration Date
Abstract
The present invention discloses methods of using the methylation status of the COX-2 gene promoter region as a biomarker for a gastric cancer patient to determine a prognosis and a treatment regimen, and to monitor the progress of a treatment regimen.
Core Innovation
The invention relates to COX-2 promoter-region hypermethylation as a methylation status biomarker for gastric cancer prognosis. Determining methylation status of the COX-2 promoter region, assessed around a predetermined number of base pairs, indicates whether the patient has a favorable or poor prognosis and predicts a probability of survival in a human gastric cancer patient.
Methylated tumors show an inverse correlation with COX-2 protein expression and are associated with less advanced clinicopathologic features. The description further reports improved time to recurrence and overall survival for methylated tumors, including in multivariate analyses.
The invention also provides uses of the methylation status for determining a prognosis and for determining a course of treatment. A course of treatment is prescribed based on the prognosis derived from the COX-2 promoter methylation status, including targeting COX-2 inhibition such as aspirin or celecoxib for hypomethylation cases, and monitoring treatment progress using baseline and interval methylation measurements.
Claims Coverage
The independent claims are directed to prognosis determination based on COX-2 promoter-region methylation status and to prescribing treatment based on that prognosis. They recite two inventive features centered on determining methylation status around a predetermined base-pair region and using hypermethylation in the COX-2 promoter region to indicate a favorable prognosis that predicts a probability of survival.
COX-2 promoter hypermethylation indicates favorable prognosis
Determining a methylation status of genomic DNA for a predetermined number of base pairs around the COX-2 promoter and determining the prognosis, wherein the prognosis predicts a probability of survival and wherein the methylation status of hypermethylation in the COX-2 promoter region indicates a favorable prognosis.
Prognosis based on COX-2 promoter methylation status for prescribing treatment
Analyzing the gastric tumor tissue sample to determine a methylation status in the COX-2 promoter region with a predetermined number of base-pairs around the promoter to determine a prognosis, wherein the prognosis predicts a probability of survival and wherein the methylation status of hypermethylation in the COX-2 promoter region indicates a favorable prognosis; and prescribing a course of treatment for the patient based on the prognosis.
The claims cover COX-2 promoter-region methylation status around a predetermined base-pair window to predict prognosis as a probability of survival, with one claim limited to prognosis determination and the other extending to prescribing treatment based on that prognosis.
Stated Advantages
Methylated tumors show improved time to recurrence.
Methylated tumors show improved overall survival, including in multivariate analyses.
Methylation status is associated with less advanced clinicopathologic features.
Methylated tumors are inversely correlated with COX-2 protein expression.
The prognosis predicts a probability of survival for the patient.
Documented Applications
Determining a prognosis for a human gastric cancer patient based on COX-2 promoter-region methylation status to predict a probability of survival.
Determining a course of treatment for a human gastric cancer patient by prescribing treatment based on the prognosis derived from COX-2 promoter-region methylation status, including COX-2 inhibition such as aspirin or celecoxib for hypomethylation cases.
Monitoring treatment progress via baseline and interval methylation measurements.
Broader applicability to other cancers.
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