Gene for predicting the prognosis for early-stage breast cancer, and a method for predicting the prognosis for early-stage breast cancer by using the same

Abstract

The present invention relates to a method for selecting a gene intended to predict the prognosis for a cancer, to the selected gene for predicting the prognosis of cancer and to a kit for predicting and a method for predicting metastasis in breast-cancer patients by using the same. In the present invention, a straight forward method is used to achieve high-reliability prediction of the patient's prognosis by analysing for the genetic characteristics of early stage breast cancer, and thus the present invention can be used to advantage in prognosis diagnosis which can reduce unnecessary anticancer therapy.

What is claimed is: 
     
         1 . A method for selecting a gene for predicting the prognosis of a cancer, comprising:
 (a) collecting cancer tissues from a patient group of which clinical information has been known;   (b) classifying the patient group into a poor prognosis group and a good prognosis group; wherein the poor prognosis group comprises patients in which metastasis occurs before a reference time point, and the good prognosis group comprises patients in which metastasis does not occur after the reference time point;   (c) obtaining expression profiles of genes from the collected cancer tissues;   (d) selecting genes showing difference in expression levels between the poor prognosis group and the good prognosis group;   (e) classifying the selected genes by expression patterns into gene clusters by use of a clustering analysis for expression patterns;   (f) selecting an expression pattern having significant correlation with certain function by performing a functional analysis to the gene clusters classified by expression patterns; and   (g) selecting a gene in genes belonging to the selected expression pattern; wherein the selected gene shows not only high expression level but also large difference in expression levels between the poor prognosis group and the good prognosis group.   
     
     
         2 . The method according to  claim 1 , wherein the clinical information in the step (a) comprises information for cancer metastasis state. 
     
     
         3 . The method according to  claim 1 , wherein the step (d) is carried out by SAM (Significant Analysis of Microarray) analysis. 
     
     
         4 . The method according to  claim 1 , wherein the cancer is breast cancer. 
     
     
         5 . The method according to  claim 4 , wherein the method further comprises, between the steps (a) and (b), the step of classifying the patient group into a patient group showing less than a reference expression level of estrogen receptor (ER) and a patient group showing more than a reference expression level of estrogen receptor (ER). 
     
     
         6 . The method according to  claim 5 , wherein the reference expression level of estrogen receptor (ER) is measured by ROC (receiver-operating characteristics) analysis using ER IHC (estrogen receptor immuno-histochemistry) results or mRNA expression level of ESR 1 (estrogen receptor 1). 
     
     
         7 . A kit for predicting metastasis risk of a breast cancer patient comprising a primer or a probe which is specifically hybridized with a nucleotide sequence selected from a group consisting of nucleotide sequences as set forth in SEQ ID NOs:1-9. 
     
     
         8 . The kit according to  claim 7 , wherein the nucleotide sequence selected from a group consisting of nucleotide sequences as set forth in SEQ ID NO:1 to SEQ ID NO:4 is high-expressed in a patient with high-risk of metastasis of breast cancer, and the nucleotide sequence selected from a group consisting of nucleotide sequences as set forth in SEQ ID NO:5 to SEQ ID NO:9 is low-expressed in a patient with high-risk of metastasis of breast cancer which shows no significant differences in expression levels of the nucleotide sequence selected from a group consisting of nucleotide sequences as set forth in SEQ ID NO:1 to SEQ ID NO:4. 
     
     
         9 . A method for predicting metastasis risk of breast cancer patient comprising measuring the expression of the nucleotide sequence selected from a group consisting of nucleotide sequences as set forth in SEQ ID NO:1 to SEQ ID NO:9. 
     
     
         10 . The method according to  claim 9 , wherein the nucleotide sequence selected from a group consisting of nucleotide sequences as set forth in SEQ ID NO:1 to SEQ ID NO:4 is high-expressed in a patient with high-risk of metastasis of breast cancer, and the nucleotide sequence selected from a group consisting of nucleotide sequences as set forth in SEQ ID NO:5 to SEQ ID NO:9 is low-expressed in a patient with high-risk of metastasis of breast cancer which shows no significant differences in expression levels of the nucleotide sequence selected from a group consisting of nucleotide sequences as set forth in SEQ ID NO:1 to SEQ ID NO:4.