Detection of Bladder Cancers
The present invention generally relates to methods of screening for cancer. Methods of the invention involve identifying a threshold parameter of a protein and of two or more nucleic acids, where the threshold parameters are indicative of the absence of cancer, conducting an assay in a sample to determine a parameter of the two or more nucleic acids and a parameter of the protein, and identifying the sample as positive for cancer if the parameters of at least one of the nucleic acids and the protein present in the sample are greater than their respective threshold parameters. In certain aspects of the invention, the nucleic acids include FGFR3, TWIST1, and NID2. In certain aspects of the invention, the protein includes MMP2 or MMP9.
1 . A method of screening for cancer, the method comprising:
identifying a threshold parameter of MMP2 or MMP9 protein and of two or more nucleic acids selected from the group consisting of FGFR3, TWIST1, and NID2, wherein said threshold parameters are indicative of the absence of cancer;
conducting an assay in a tissue or body fluid sample in order to determine a parameter of two or more nucleic acids selected from the group consisting of nucleic acid encoding FGFR3, TWIST1, and NID2;
determining a parameter of MMP2 or MMP9 protein in said sample;
identifying said sample as positive for cancer if the parameters of at least one of said nucleic acids and the parameter of said protein present in said sample are greater than their respective threshold parameters.
2 . The method of claim 1 , wherein the cancer is a bladder cancer.
3 . The method of claim 1 , wherein the sample is selected from urine or blood.
4 . The method of claim 1 , wherein the nucleic acid is DNA or RNA.
5 . The method of claim 1 , wherein the parameter comprises a methylation pattern in the one or more of said nucleic acids.
6 . The method of claim 1 , wherein the parameter comprises a mutation in at least one of said nucleic acids.
7 . The method of claim 6 , wherein said mutation is selected from a loss of heterozygosity, a single nucleotide polymorphism, a deletion, an insertion, a rearrangement, and a translocation.
8 . The method of claim 1 , wherein the parameter comprises a level of protein expression of said protein.
9 . The method of claim 1 , wherein the parameter comprises a level of gene expression of at least one of said nucleic acids.
10 . The method of claim 1 , wherein said assay comprises sequencing said nucleic acid.
11 . The method of claim 1 , wherein said conducting and determining steps comprise
obtaining a sample comprising two or more said nucleic acids and MMP-2 or MMP-9 protein;
introducing an aptamer that binds to MMP-2 or MMP-9 protein in the sample;
removing unbound aptamer; and
conducting a single assay, wherein the assay detects both said nucleic acids and said protein, the assay comprising: performing a sequencing reaction on the two or more said nucleic acid and the aptamer, thereby detecting the nucleic acid and the aptamer in the sample.
12 . The method of claim 11 , wherein said assay is a single molecule assay.
13 . The method of claim 12 , wherein said single molecule assay is an ion semiconductor sequencing assay.