Cancer biomarkers and methods of use thereof

Abstract

The present invention provides detection methods for detecting a pre-cancerous epithelial cell signature. The present invention further provides reagents for use in the detection methods. A subject detection method is useful in various imaging, diagnostic, prognostic, and patient monitoring methods, which are also provided.

1 . (canceled) 
     
     
         2 . A composition comprising: at least two imaging agents for detecting a risk of developing cancer, wherein the at least two imaging agents comprise:
 at least one first imaging agent that binds to a first mammary epithelial cell structure, the first mammary epithelial cell structure selected from the group consisting of:   a p16 protein; and   an mRNA encoding the p16 protein,   wherein the first imaging agent comprises an antibody, a nucleic acid, a protein or a carbohydrate; and   at least one second imaging agent that binds to a second mammary epithelial cell structure, the second mammary epithelial cell structure selected from the group consisting of:   a Ki67 protein; and   an mRNA encoding the Ki67 protein,
 wherein the second imaging agent comprises an antibody, a nucleic acid, a protein or a carbohydrate, 
   wherein each of the first imaging agent and the second imaging agent comprises a selective binding moiety and a detectable label, and   wherein the second imaging agent is different from the first imaging agent.   
     
     
         3 . The composition of  claim 2 , further comprising at least one third imaging agent that binds to a third mammary epithelial cell structure, the third mammary epithelial cell structure selected from the group consisting of:
 a COX-2 protein; and   an mRNA encoding the COX-2 protein,   wherein the third imaging agent comprises an antibody, a nucleic acid, a protein or a carbohydrate.   
     
     
         4 . The composition of  claim 2 , wherein the at least one first imaging agent comprises an antibody that binds to the p16 protein, and wherein the at least one second imaging agent comprises an antibody that binds to the Ki67 protein. 
     
     
         5 . The composition of  claim 3 , wherein the at least one first imaging agent comprises an antibody that binds to the p16 protein, and wherein the at least one second imaging agent comprises an antibody that binds to the Ki67 protein. 
     
     
         6 . The composition of  claim 3 , wherein the at least one first imaging agent comprises an antibody that binds to the p16 protein, and wherein the at least one third imaging agent comprises an antibody that binds to the COX-2 protein. 
     
     
         7 . The composition of  claim 3 , wherein the at least one second imaging agent comprises an antibody that binds to the Ki67 protein, and wherein the at least one third imaging agent comprises an antibody that binds to the COX-2 protein. 
     
     
         8 . A kit for determining a risk of developing breast cancer based on detecting a mammary epithelial cell signature with the use of a plurality of reagents, the kit comprising:
 a first reagent configured to detect:
 (a) a presence, level, or presence and level of at least a p16 protein; or 
 (b) a presence, level, or presence and level of at least an mRNA encoding the p16 protein, and 
 a second reagent configured to detect: 
 (a) a presence, level, or presence and level of at least a Ki67 protein; or 
 (b) a presence, level, or presence and level of at least an mRNA encoding the Ki67 protein, 
   wherein the first reagent and the second reagent comprises an antibody, a nucleic acid, a protein, or a carbohydrate.   
     
     
         9 . The kit of  claim 8 , wherein the first reagent comprises one or more antibody or nucleic acid probes, wherein the antibody or nucleic acid probe is specific to one or more of:
 the presence, level, or presence and level of the at least p16 protein;   the presence, level, or presence and level of the at least mRNA encoding the p16 protein;   the presence, level, or presence and level of the at least Ki67 protein; and   the presence, level, or presence and level of the at least mRNA encoding the Ki67 protein.   
     
     
         10 . The kit of  claim 8 , wherein:
 the first reagent comprises a first nucleic acid probe that binds to an mRNA that encodes the Ki67 protein; and   the second reagent comprises a second nucleic acid probe that binds to an mRNA that encodes the p16 protein.   
     
     
         11 . The kit of  claim 10 , wherein the first nucleic acid probe is coupled to a first detectable label, and wherein the second nucleic acid probe is coupled to a second detectable label that is different from the first detectable label. 
     
     
         12 . The kit of  claim 10 , further comprising a third nucleic acid probe that binds to an mRNA that encodes a COX-2 protein, wherein the third nucleic acid probe is coupled to a detectable label. 
     
     
         13 . The kit of  claim 8 , further comprising a third reagent that binds to a COX-2 protein, wherein the second reagent binds to the Ki67 protein, wherein the first reagent binds to the p16 protein, and wherein each of the reagents comprises at least one of an antibody, a nucleic acid, a protein, or a carbohydrate. 
     
     
         14 . The kit of  claim 8 , wherein at least one of the first or second reagents comprises an antibody is coupled to a detectable label selected from the group consisting of gold, a fluorescent protein, a chromogenic protein, a fluorescent dye, an enzyme, a biotin, a radioisotope and any combinations thereof. 
     
     
         15 . A combination of at least three imaging agents each of which binds to a mammary epithelial cell structure, wherein the at least three different imaging agents comprises:
 at least one first imaging agent that binds to
 a p16 protein; or 
 an mRNA encoding the p16 protein; 
   at least one second imaging agent that binds to:
 a Ki67 protein; or 
 an mRNA encoding the Ki67 protein; and 
   at least one third imaging agent that binds to
 a Cox-2 protein; or 
 a Cox-2 mRNA encoding the Cox-2 protein, 
   wherein each of the at least three different imaging agents comprises a selective binding moiety and a detectable label.   
     
     
         16 . The combination of  claim 15 , wherein the at least one first imaging agent comprises an antibody that binds to the p16 protein, and wherein the at least one second imaging agent comprises an antibody that binds to the Ki67 protein. 
     
     
         17 . The combination of  claim 15 , wherein the at least one first imaging agent comprises an antibody that binds to the p16 protein, and wherein the at least one third imaging agent comprises an antibody that binds to the COX-2 protein. 
     
     
         18 . The combination of  claim 15 , wherein the at least one second imaging agent comprises an antibody that binds to the Ki67 protein, and wherein the at least one third imaging agent comprises an antibody that binds to the COX-2 protein.