Gene and gene expressed protein targets depicting biomarker patterns and signature sets by tumor type

Abstract

Provided herein are methods and systems for identifying a therapeutic for an individual, such as a therapeutic not previously identified for treating the individual. The therapeutic can be identified by molecular profiling, such as determining the biomarker patterns or signature sets of a biological sample of an individual.

What is claimed is: 
     
         1 . A method for selecting one or more therapeutic agent for an individual suffering ovarian cancer that has previously been administered one therapeutic comprising:
 (a) obtaining a tumor sample from the individual, and measuring expression level of androgen receptor (AR) in the sample;   (b) comparing said expression level obtained in (a) to a predetermined reference level;   (c) identifying one or more therapeutic agent specific for AR, if AR is differentially expressed as compared to the reference level, wherein said individual has not been previously treated with said one or more therapeutic agent; thereby selecting one or more therapeutic for the individual suffering from ovarian cancer.   
     
     
         2 . The method of  claim 1 , wherein said expression is determined by analysis of mRNA and/or protein. 
     
     
         3 . The method of  claim 1 , wherein said determining an expression level is by immunohistochemistry (IHC) analysis, microarray analysis, in-situ hybridization (ISH), real-time PCR, or a combination thereof. 
     
     
         4 . The method of  claim 1 , wherein said determining an expression level comprises use of IHC and microarray. 
     
     
         5 . The method of  claim 3 , wherein said microarray analysis comprises using an expression microarray, a comparative genomic hybridization (CGH) microarray, a single nucleotide polymorphism (SNP) microarray, a proteomic array or an antibody array. 
     
     
         6 . The method of  claim 3 , wherein said microarray analysis comprises identifying whether said gene is up-regulated or down-regulated relative to a reference with a significance of p<0.001. 
     
     
         7 . The method of  claim 3 , wherein said IHC analysis comprises determining whether 30% or more of said sample is +2 or greater in staining intensity. 
     
     
         8 . The method of  claim 1 , further comprising detecting in the sample a mutation, polymorphism, deletion, or insertion of additional markers comprising SPARC, TOP2A, PTEN, CD52, RRM1, DNMT3B, RRM2, SRC, RRM2B, SSTR2, FLT1, SSTR5, BRCA1, DHFR, KDR, and EPHA2. 
     
     
         9 . The method of  claim 8 , wherein said detecting comprises performing ISH, FISH, PCR, real-time PCR, sequencing, or a combination thereof. 
     
     
         10 . The method of  claim 1 , further comprising detecting in the sample a mutation, polymorphism, deletion, or insertion of additional markers comprising HSP90, Survivin, SSTR3, VEGFA, SSTR4, HSP90AA1, YES1, RXRG, and LCK. 
     
     
         11 . The method of  claim 8 , wherein said expression levels of SPARC, TOP2A, RRM1 and PTEN are determined by IHC. 
     
     
         12 . The method of  claim 8 , wherein said expression levels of CD52, RRM1 and BRCA1 are mRNA expression levels. 
     
     
         13 . A method for treating an individual comprising:
 (a) obtaining a tumor sample from the individual suffering from ovarian cancer;   (b) contacting the sample with an antibody specific to AR to determine expression level of AR present in the sample;   (c) comparing the expression level in (b) with a pre-determined reference to identify differential expression of AR compared to the reference; and   (d) administering to the individual a therapeutic agent specific for AR, if the differential expression of AR is up-regulated as compared to the reference; thereby treating the individual.   
     
     
         14 . The method of  claim 13 , wherein said expression level is determined by analysis of mRNA and/or protein. 
     
     
         15 . The method of  claim 13 , wherein said determining an expression level is by immunohistochemistry (IHC) analysis, microarray analysis, in-situ hybridization (ISH), real-time PCR, or a combination thereof. 
     
     
         16 . The method of  claim 13 , wherein said determining an expression level comprises use of IHC and microarray. 
     
     
         17 . The method of  claim 13 , wherein said microarray analysis comprises using an expression microarray, a comparative genomic hybridization (CGH) microarray, a single nucleotide polymorphism (SNP) microarray, a proteomic array or an antibody array. 
     
     
         18 . The method of  claim 13 , wherein said microarray analysis comprises identifying whether said gene is up-regulated or down-regulated relative to a reference with a significance of p<0.001. 
     
     
         19 . The method of  claim 13 , wherein said IHC analysis comprises determining whether 30% or more of said sample is +2 or greater in staining intensity. 
     
     
         20 . The method of  claim 13 , further comprising detecting in the sample a mutation, polymorphism, deletion, or insertion of additional markers comprising SPARC, TOP2A, PTEN, CD52, RRM1, DNMT3B, RRM2, SRC, RRM2B, SSTR2, FLT1, SSTR5, BRCA1, DHFR, KDR, and EPHA2. 
     
     
         21 . The method of  claim 20 , wherein said detecting comprises performing ISH, FISH, PCR, real-time PCR, sequencing, or a combination thereof. 
     
     
         22 . The method of  claim 13 , further comprising detecting in the sample a mutation, polymorphism, deletion, or insertion of additional markers comprising HSP90, Survivin, SSTR3, VEGFA, SSTR4, HSP90AA1, YES1, RXRG, and LCK. 
     
     
         23 . The method of  claim 20 , wherein said expression levels of SPARC, TOP2A, RRM1 and PTEN are determined by IHC. 
     
     
         24 . The method of  claim 20 , wherein said expression levels of CD52, RRM1 and BRCA1 are mRNA expression levels. 
     
     
         25 . A method of selecting a subject for treatment comprising,
 (a) obtaining a tumor sample from the subject, wherein the subject has been previously treated with one or more therapeutic for ovarian cancer;   (b) determining expression of level of AR in the tumor sample;   (c) comparing the expression level to a predetermined reference to measure a differential expression of AR compared to the reference; and   (d) selecting the subject for treatment with an AR specific therapeutic if the differential expression of AR is up-regulated as compared to the reference; thereby selecting the subject for treatment.   
     
     
         26 . The method of  claim 25 , wherein said expression level is determined by analysis of mRNA and/or protein. 
     
     
         27 . The method of  claim 25 , wherein said determining an expression level is by immunohistochemistry (IHC) analysis, microarray analysis, in-situ hybridization (ISH), real-time PCR, or a combination thereof. 
     
     
         28 . The method of  claim 25 , wherein said determining an expression level comprises use of IHC and microarray. 
     
     
         29 . The method of  claim 25 , wherein said microarray analysis comprises using an expression microarray, a comparative genomic hybridization (CGH) microarray, a single nucleotide polymorphism (SNP) microarray, a proteomic array or an antibody array. 
     
     
         30 . The method of  claim 25 , wherein said microarray analysis comprises identifying whether said gene is up-regulated or down-regulated relative to a reference with a significance of p<0.001. 
     
     
         31 . The method of  claim 25 , wherein said IHC analysis comprises determining whether 30% or more of said sample is +2 or greater in staining intensity. 
     
     
         32 . The method of  claim 25 , further comprising detecting in the sample a mutation, polymorphism, deletion, or insertion of additional markers comprising SPARC, TOP2A, PTEN, CD52, RRM1, DNMT3B, RRM2, SRC, RRM2B, SSTR2, FLT1, SSTR5, BRCA1, DHFR, KDR, and EPHA2. 
     
     
         33 . The method of  claim 32 , wherein said detecting comprises performing ISH, FISH, PCR, real-time PCR, sequencing, or a combination thereof. 
     
     
         34 . The method of  claim 25 , further comprising detecting in the sample a mutation, polymorphism, deletion, or insertion of additional markers comprising HSP90, Survivin, SSTR3, VEGFA, SSTR4, HSP90AA1, YES1, RXRG, and LCK. 
     
     
         35 . The method of  claim 32 , wherein said expression levels of SPARC, TOP2A, RRM1 and PTEN are determined by IHC. 
     
     
         36 . The method of  claim 32 , wherein said expression levels of CD52, RRM1 and BRCA1 are mRNA expression levels.