Urine gene expression ratios for detection of cancer

Abstract

This invention relates to methods for determining the presence of cancer in a subject based on the analysis of the expression levels of an under-expressed tumour marker (TM) and at least one other TM. Specifically, this invention relates to the determination of a cancer, particularly bladder cancer, by performing ratio, regression or classification analysis of the expression levels of at least one under-expressed TM, particularly an under-expressed bladder TM (BTM), and at least one over-expressed TM, particularly an over-expressed BTM. In various aspects, the invention telates to kits and devices for carrying out these methods.

1 . A method for determining the presence of a cancer in a subject, comprising:
 (a) providing a sample from the subject;   (b) detecting the expression level of at least two tumor marker (TM) family members in said sample, wherein at least one TM is an under-expressed TM;   (c) establishing whether the patient has cancer according to a predetermined threshold, wherein the predetermined threshold is established by determining the ratio of expression of said TMs, or by performing regression or classification analysis on the TM expression values.   
     
     
         2 . The method of  claim 1 , wherein the TM is a bladder tumor marker (BTM). 
     
     
         3 . The method of  claim 1 , wherein said cancer is bladder cancer. 
     
     
         4 . The method of  claim 1 , wherein at least one of the TMs is an over-expressed TM. 
     
     
         5 . The method according to  claim 1 , wherein the at least one under-expressed TM is a BTM selected from the group listed in  FIG. 3 . 
     
     
         6 . The method according to  claim 1 , wherein the at least one under-expressed TM is a BTM selected from the group listed in  FIG. 4 . 
     
     
         7 . The method according to  claim 4 , wherein the over-expressed TM is BTM selected from the group listed in  FIG. 11  or  FIG. 12 . 
     
     
         8 . The method of  claim 1 , wherein said step of detecting is carried out by detecting expression of TM mRNA. 
     
     
         9 . The method of  claim 1 , wherein said step of detecting is carried out by detecting expression of a TM protein. 
     
     
         10 . The method of  claim 1 , wherein said step of detecting is carried out by detecting expression of a TM peptide. 
     
     
         11 . The method of  claim 1 , wherein the sample is any one of biopsy, blood, serum, peritoneal washes, cerebrospinal fluid, urine and stool samples 
     
     
         12 . A device for detecting a TM, comprising:
 a substrate having a TM capture reagent thereon; and   a detector associated with said substrate, said detector capable of detecting a TM associated with said capture reagent, wherein the TM is an under-expressed TM.   
     
     
         13 . The device of  claim 12 , wherein the TM is a BTM. 
     
     
         14 . The device of  claim 12 , wherein said TM capture reagent is an oligonucleotide. 
     
     
         15 . The device of  claim 12 , wherein said TM capture reagent is an antibody. 
     
     
         16 . The device of  claim 12 , wherein the TM is a BTM selected from the group listed in  FIG. 3 . 
     
     
         17 . The device of  claim 12 , wherein the TM is a BTM selected from the group listed in  FIG. 4 . 
     
     
         18 . A kit for determining the presence of a cancer in a subject, comprising:
 a substrate;   at least two TM capture reagents, wherein at least one TM is an under-expressed TM; and   instructions for use.   
     
     
         19 . The Kit of  claim 18 , wherein the TM is a BTM. 
     
     
         20 . The kit of  claim 18 , wherein said TM capture reagent is a TM-specific oligonucleotide. 
     
     
         21 . The kit of  claim 18 , wherein said TM capture reagent is a TM-specific antibody. 
     
     
         22 . The kit of  claim 18 , wherein the under-expressed TM is a BTM selected from the group listed in  FIG. 3 . 
     
     
         23 . The kit of  claim 18 , wherein the under-expressed TM is a BTM selected from the group listed in  FIG. 4 . 
     
     
         24 . The kit according to  claim 20 , wherein at least one TM is an over-expressed TM. 
     
     
         25 . The kit according to claim  263 , wherein the over-expressed TM is a BTM selected from the group listed in  FIG. 11  or  FIG. 12 .