Gene Relating to Estimation of Postoperative Prognosis for Breast Cancer

Abstract

It is intended to provide a system of predicting the postoperative prognosis in a patient with breast cancer from the viewpoint of gene expression based on the data obtained by genome-wide and comprehensive analysis on gene expression in breast cancer. Expression of human genes is comprehensively analyzed by using a DNA microarray and gene expression functions in various breast cancer conditions are compared, thereby establishing a system of predicting the postoperative prognosis of breast cancer.

1 . A gene consisting of at least one of the following definitions correlated with prediction of the postoperative prognosis of breast cancer;
 1) a marker gene group capable of establishing classification of genes from breast cancer patients died within 5 years after a surgical operation (5y-D group) and genes from patients survived free of disease for several years or more after the operation (5y-S group), depending on their expression functions, in estrogen receptor-negative breast cancer,   2) a marker gene group capable of establishing classification of genes from n0 breast cancer patients recurred within 5 years after an operation (5Y-R group) and genes from patients survived free of disease for 5 years or more after the operation (5Y-F group), depending on their expression functions, in (node-negative) (n0) breast cancer with no metastasis to a lymph node in the operation,   3) a marker gene group capable of establishing classification of genes from breast cancer patients died within 5 years after a surgical operation (5D group) and genes from patients survived free of disease for several years or more after the operation (5S group), depending on their expression functions, in primary breast cancer.   
     
     
         2 . A gene selected from the following sequences correlated with prediction of the postoperative prognosis of primary breast cancer;
 pro-alpha-1 type 3 collagen (PIIIP),   complement component Clr,   dihydropyrimidinase-like 3 (DPYSL3),   protein tyrosine kinase 9-like (PTK9L),   carboxypeptidase E (CPE),   alpha-tubulin,   beta-tubulin,   heat shock protein HSP 90-alpha gene,   malate dehydrogenase,   NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3 (NDUFB3).   
     
     
         3 . A gene selected from the following sequences highly expressed in a group of good prognosis correlated with prediction of the postoperative prognosis of primary breast cancer;
 pro-alpha-1 type 3 collagen (PIIIP),   complement component Clr,   dihydropyrimidinase-like 3 (DPYSL3),   protein tyrosine kinase 9-like (PTK9L),   carboxypeptidase E (CPE),   alpha-tubulin,   beta-tubulin.   
     
     
         4 . A gene selected from the following sequences highly expressed in a group of bad prognosis correlated with prediction of the postoperative prognosis of primary breast cancer; heat shock protein HSP 90-alpha gene,
 malate dehydrogenase,   NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3 (NDUFB3).   
     
     
         5 . A gene selected from the following sequences correlated with prediction of the postoperative prognosis, in (node-negative)(n0) breast cancer with no metastasis to a lymph node in operation;
 AF058701/DNA polymerase zeta catalytic subunit (REV3),   AM066764/lectin, galactoside-binding, soluble, 1 (galectin 1),   x15940/ribosomal protein L31.,   Hs.94653/neurochondrin (KIAA0607),   M13436/ovarian beta-A-inhibin,   Hs.5002/copper chaperone for superoxide dismutase; CCS,   D67025/proteasome (prosome, macropain) 26S subunit, non-ATPase, 3,   M80469/MHC class I HLA-J gene,   Hs.4864/ESTs,   Hs.106326/ESTs.   
     
     
         6 . A gene selected from the following sequences highly expressed in a group of bad prognosis correlated with prediction of the postoperative prognosis, in (node-negative) (n0) breast cancer with no metastasis to a lymph node in operation;
 AF058701/DNA polymerase zeta catalytic subunit (REV3),   AM066764/lectin, galactoside-binding, soluble, 1 (galectin 1),   x15940/ribosomal protein L31.   
     
     
         7 . A gene selected from the following sequences highly expressed in a group of good prognosis correlated with prediction of the postoperative prognosis, in (node-negative)(n0) breast cancer with no metastasis to a lymph node in operation;
 Hs.94653/neurochondrin (KIAA0607),   M13436/ovarian beta-A-inhibin,   Hs.5002/copper chaperone for superoxide dismutase; CCS,   D67025/proteasome (prosome, macropain) 26S subunit, non-ATPase, 3,   M80469/MHC class I HLA-J gene,   Hs.4864/ESTs,   Hs.106326/ESTs.   
     
     
         8 . A gene selected from the following sequences correlated with prediction of the postoperative prognosis, in estrogen receptor-negative breast cancer;
 Hs.108504/FLJ20113/ubiquitin-specific protease otubain 1   Hs.146550/MYH9/myosin, heavy polypeptide 9, non-muscle   Hs.194691/RAI3/retinoic acid induced 3   Hs. 1975/TDRD3/tudor domain containing 3   Hs.203952/TRRAP/transformation/transcription domain-associated protein   Hs.278607/GSA7/ubiquitin activating enzyme E1-like protein   Hs.429/ATP5G3/
 ATP synthase, H+ transporting, mitochondrialF0complex, subunitc (subunit9) isoform3 
   Hs.75305/AIP/aryl hydrocarbon receptor interacting protein   Hs.81170/PIM1/pim-1 oncogene   Hs.99987/ERCC2/
 excision repair cross-complementing rodent repair deficiency, complementation group 2 
   Y12781/Transducin (beta) like 1 protein   Hs.104417/KIAA1205 protein   cl.21783/Hypothetical protein   Hs.112628/Hypothetical protein: MGC43581   Hs.170345/Hypothetical protein FLJ13710   Hs.53996/weakly similar to zinc finger protein 135   Hs.55422/Hypothetical protein   Hs.112718/EST   Hs.115880/EST   Hs.126495/EST.   
     
     
         9 . A gene selected from  claim 8 , as a gene highly expressed in a group of bad prognosis. 
     
     
         10 . A probe specific to the gene according to any one of  claims 1  to  9 . 
     
     
         11 . A DNA microarray carrying thereon the gene and/or probe according to any one of  claims 1  to  10 . 
     
     
         12 . The microarray according to  claim 11 , wherein the DNA microarray is a fiber type microarray. 
     
     
         13 . A method of inspecting the postoperative prognosis of breast cancer using as a marker the gene and/or probe according to any one of  claims 1  to  10 . 
     
     
         14 . A method of inspecting the postoperative prognosis of breast cancer using the microarray according to  claim 11  or  12 . 
     
     
         15 . A method of screening cancer therapeutic medicines for controlling the postoperative prognosis of breast cancer using as a marker the gene and/or probe according to any one of  claims 1  to  10 . 
     
     
         16 . A method of screening cancer therapeutic medicines for controlling the postoperative prognosis of breast cancer using the microarray according to  claim 11  or  12 . 
     
     
         17 . A diagnosis kit for the postoperative prognosis of breast cancer containing a reagent using as a marker the gene and/or probe according to any one of  claims 1  to  10 . 
     
     
         18 . The diagnosis kit according to  claim 17 , wherein the kit comprises a microarray. 
     
     
         19 . The diagnosis kit according to  claim 18 , wherein the microarray is a fiber type microarray.