Long interspersed nuclear elements (line-1) and alu hypomethylation as biomarkers for colorectal cancer metastasis
AssigneeBaylor Research Institute
InventorsAjay Goel, C. Richard Boland, Keun Hur
Life of this patent
Estimating the term…
Abstract
A method for determining a colorectal cancer metastasis in a human subject suffering from a primary colorectal cancer (CRC) is described herein. The method of the present invention comprises the steps of: i) identifying the human subject suffering from the primary CRC, ii) obtaining one or more biological samples from the human subject, iii) detecting a methylation level of Alu, LINE-1, or both in the one or more biological samples, and iv) increasing the level of the colorectal metastatic stage in the human subject when the methylation level of Alu, LINE-1 is lower compared to a corresponding control methylation level of Alu, LINE-1.
Claims26
A method for determining a colorectal cancer metastasis in a human subject comprising the steps of:
- obtaining one or more biological samples from the human subject;
- detecting a methylation level of Alu, LINE-1, or both in the one or more biological samples;
- and
- increasing the diagnosis of the level of the colorectal metastatic stage in the human subject when the methylation level of Alu, LINE-1 is lower compared to a corresponding control methylation level of Alu, LINE-1.
A biomarker for detecting a colorectal cancer metastasis in a human subject suffering from primary colorectal cancer comprising:
- a methylation level of Alu, LINE-1, or both for comparison to a corresponding control methylation level of Alu, LINE-1, or both, wherein a lower Alu, a lower LINE-1 methylation or both are indicative of a higher colorectal metastatic stage in the human subject.
A kit for determining a stage of colorectal metastasis comprising:
- one or more biomarker to determine a methylation level of Alu, LINE-1, or both;
- and
- instructions for their use in diagnosing presence or risk for colorectal cancer metastasis, wherein the instructions comprise providing step-by-step instructions for comparing the methylation level of Alu, LINE-1, or both in one or more samples from a subject suffering from colorectal cancer to a corresponding control methylation level of Alu, LINE-1, or both in one or more samples obtained from a normal subject, wherein the normal subject is a subject not suffering from metastatic colorectal cancer, wherein a lower Alu, lower LINE-1 methylation or both are indicative of colorectal liver metastatic stage in the human subject.
A method for selecting a cancer therapy for a patient diagnosed with metastatic colorectal cancer comprising the steps of:
- determining an overall methylation level of Alu, LINE-1, or both in one or more cells obtained from a biological sample of the subject, wherein an Alu methylation level and an LINE-1 methylation level are lower compared to the corresponding control methylation level is indicative of an advancement in the stage of the colorectal cancer from a lower to a higher stage;
- and
- selecting the cancer therapy based on the determination of the increase in the stage of the colorectal cancer in the patient.
A method of performing a clinical trial to evaluate a candidate drug believed to be useful in treating colorectal liver metastasis, the method comprising:
- a) determining a stage of the metastatic colorectal cancer by a method comprising the steps of:
- determining an overall methylation level of Alu, LINE-1, or both in one or more cells obtained from a biological samples of the subject, wherein Alu methylation and LINE-1 methylation in liver metastatis were significantly lower compared to the corresponding matched primary CRC is indicative of a stage of the colorectal liver metastasis;
- b) administering a candidate drug to a first subset of the patients, and
- a placebo to a second subset of the patients;
- a comparable drug to a second subset of the patients;
- or
- a drug combination of the candidate drug and another active agent to a second subset of patients;
- c) repeating step a) after the administration of the candidate drug or the placebo, the comparable drug or the drug combination;
- and
- d) monitoring a change in the liver metastases that is statistically significant as compared to any reduction occurring in the second subset of patients, wherein a statistically significant reduction indicates that the candidate drug is useful in treating said disease state.
A method for determining a colorectal metastatic stage in a human subject suffering from a primary colorectal cancer (CRC) comprising the steps of:
- identifying the human subject suffering from the primary CRC;
- obtaining one or more biological samples from the human subject;
- detecting a methylation level of Alu, LINE-1, or both in the one or more biological samples;
- and
- increasing the level of the colorectal metastatic stage in the human subject when the methylation level of Alu, LINE-1 is lower compared to a corresponding control methylation level of Alu, LINE-1.
Dependencies are inferred from the claim text.