DNA methylation biomarkers for bladder cancer
A method for the prediction, prognosis and/or diagnosis of bladder cancer or bladder cancer recurrence in a subject, the method includes: providing a test sample from the subject; measuring DNA methylation levels of at least a portion of two or more polynucleotides selected from the group consisting of HOXA9, SOXI, NPY, IRAK3, L1-MET, and Z02 in the test sample; calculating a risk score based on the measured DNA methylation levels, comparing the calculated risk score to a cut-off value derived from a reference DNA methylation profile based on DNA methylation levels of the one or more biomarkers derived from a control group, members of which had bladder cancer; and based on the comparison calculated risk score to the cut-off value, determining at least one of: (1) whether bladder cancer has recurred; (2) whether there is likelihood that the bladder cancer will recur; and (3) whether the patient has bladder cancer.
1. A method for providing a treatment of or bladder cancer recurrence in a human subject, the method comprising:
providing a test sample from the subject, wherein the test sample is urine;
measuring DNA methylation levels of at least a portion of polynucleotides in the test sample, wherein the polynucleotides comprise SOX1, IRAK3 and L1-MET;
calculating a risk score based on the measured DNA methylation levels,
comparing the calculated risk score to a cut-off value derived from a reference DNA methylation profile based on DNA methylation levels of the polynucleotides derived from a control group, members of which had bladder cancer;
based on the comparison of the calculated risk score to the cut-off value, determining whether bladder cancer has recurred or whether there is likelihood that the bladder cancer will recur; and
providing a cancer treatment to the subject, wherein the cancer treatment is tumor resection, chemotherapy or immunotherapy.
2. The method of claim 1 , wherein the polynucleotides further comprise HOXA9.
3. The method of claim 1 , further comprising: extracting DNA from the test sample, bisulfate conversion, and PCR amplification.
4. The method of claim 1 , wherein DNA methylation levels is a percentage of methylated cytosines, defined as a number of methylated cytosines divided by the sum of methylated and unmethylated cytosines.
5. The method of claim 1 , wherein the urine comprises urine sediment.
6. The method of claim 1 , wherein the risk score is calculated using a logistic regression analysis.
7. The method of claim 1 , wherein the risk score is calculated using a multi-variate equation.
8. The method of claim 1 , wherein the polynucleotides consist of SOX1, IRAK3 and L1-MET.