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.

1 . A method for identifying one or more therapeutic agent for an individual with a cancer comprising:
 (a) determining an expression level of two or more markers from a biological sample of said individual, wherein said markers are selected from the group consisting of SPARC, TOP2A, PTEN, CD52, HSP90, Survivin, RRM1, SSTR3, DNMT3B, VEGFA, SSTR4, RRM2, SRC, RRM2B, HSP90AA1, SSTR2, FLT1, SSTR5, YES1, BRCA1, RRM1, DHFR, KDR, EPHA2, RXRG, and LCK;   (b) comparing said expression level to a predetermined reference level; and   (c) identifying one or more therapeutic agent specific for one or more of said two or more markers based on said comparison, wherein said individual has not been previously treated with said one or more therapeutic agent, thereby identifying the one or more therapeutic agent for treating the individual.   
     
     
         2 . The method of  claim 1 , wherein said expression level for at least two of said two or more markers is determined by analysis of mRNA and 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 determining an expression level of at least two of said two or more genes is by 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 are +2 or greater in staining intensity. 
     
     
         8 . The method of  claim 1 , further comprising identifying a mutation, polymorphism, deletion, or insertion in at least one of said two or more markers. 
     
     
         9 . The method of  claim 8 , wherein said identifying is by IHC analysis, microarray analysis, ISH, FISH, PCR, real-time PCR, sequencing, or a combination thereof. 
     
     
         10 . The method of  claim 1 , wherein said determining comprises at least three markers from said group. 
     
     
         11 . The method of  claim 1 , wherein said determining comprises at least five markers from said group. 
     
     
         12 . The method of  claim 1 , wherein said two or more markers comprise two or more of HSP90, Survivin, RRM1, SSTR3, DNMT3B, VEGFA, SSTR4, RRM2, SRC, RRM2B, HSP90AA1, SSTR2, FLT1, SSTR5, YES1, BRCA1, RRM1, DHFR, KDR, EPHA2, RXRG, and LCK. 
     
     
         13 . The method of  claim 1 , wherein said two or more markers comprise two or more of BRCA1, RRM1, SRC, DHFR, and KDR. 
     
     
         14 . The method of  claim 1 , wherein said two or more markers comprise BRCA1, RRM1, SRC, DHFR, and KDR. 
     
     
         15 . The method of  claim 1 , wherein said two or more markers comprise SPARC, TOP2A and PTEN. 
     
     
         16 . The method of  claim 15 , wherein said SPARC, TOP2A and PTEN are determined by IHC. 
     
     
         17 . The method of  claim 1 , wherein said two or more markers comprise CD52. 
     
     
         18 . The method of  claim 17 , wherein said level of CD52 is an mRNA expression level. 
     
     
         19 . The method of  claim 1 , wherein the cancer comprises metastatic cancer. 
     
     
         20 . The method of  claim 1 , wherein the cancer comprises a cancer of one or more of adipose tissue, adrenal cortex, adrenal gland, adrenal gland-medulla, appendix, bladder, blood vessel, bone, bone cartilage, brain, breast, cartilage, cervix, colon, colon sigmoid, dendritic cells, skeletal muscle, enodmetrium, esophagus, fallopian tube, fibroblast, gallbladder, kidney, larynx, liver, lung, lymph node, melanocytes, mesothelial lining, myoepithelial cells, osteoblasts, ovary, pancreas, parotid, prostate, salivary gland, sinus tissue, skeletal muscle, skin, small intestine, smooth muscle, stomach, synovium, joint lining tissue, tendon, testis, thymus, thyroid, uterus, and uterus corpus. 
     
     
         21 . The method of  claim 1 , wherein the cancer comprises a cancer of one or more of the accessory, sinuses, middle ear, inner ear, adrenal glands, appendix, hematopoietic system, bones and joints, spinal cord, breast, cerebellum, cervix uteri, connective and soft tissue, corpus uteri, esophagus, eye, nose, eyeball, fallopian tube, extrahepatic bile ducts, other mouth, intrahepatic bile ducts, kidney, appendix-colon, larynx, lip, liver, lung and bronchus, lymph nodes, cerebral, spinal, nasal cartilage excl. retina, oropharynx, endocrine glands, female genital, ovary, pancreas, penis, scrotum, pituitary gland, pleura, prostate gland, rectum, renal, pelvis, ureter, peritoneum, salivary gland, skin, small intestine, stomach, testis, thymus, thyroid gland, tongue, urinary bladder, uterus, vagina, labia, and vulva. 
     
     
         22 . The method of  claim 1 , wherein said predetermined reference level is a normal reference level. 
     
     
         23 . The method of  claim 22 , wherein said identifying comprises identifying markers with differential expression levels based on said comparison.