Detecting pax2 for the diagnosis of breast cancer

Abstract

A method for monitoring breast conditions in a subject is disclosed. The method comprises determining a Paired Box 2 gene-to-beta defensin- 1 gene (PAX2-to-DEFB1) expression ratio (the “Donald Predictive Factor” or “DPF”) in cells obtained from the breast of the subject, wherein the PAX2-to-DEFB1 expression ratio is correlated with breast conditions. Also disclosed is a kit for monitoring breast conditions and determining drug resistance.

1 . A method for monitoring breast conditions in a subject, comprising:
 determining a Paired Box 2 gene-to-beta defensin-1 gene (PAX2-to-DEFB1) expression ratio in cells obtained from the breast of the subject,   wherein the PAX2-to-DEFB1 expression ratio is correlated with breast conditions.   
     
     
         2 . The method of  claim 1 , wherein a PAX 2-to-DEFB1 expression ratio of 100:1 or higher is indicative of the presence of breast cancer in the subject, and a PAX2-to-DEFB1 expression ratio less than 100:1 is indicative of the presence of non-cancerous or pre-cancerous breast condition in the subject. 
     
     
         3 . The method of  claim 2 , wherein the pre-cancerous breast condition is mammary intraepithelial neoplasia. 
     
     
         4 . The method of  claim 1 , wherein the determining step comprises:
 determining the expression level of PAX2 gene relative to the expression level of a control gene;   determining the expression level of DEFB1 gene relative to the expression level of the same control gene; and   determining the PAX2-to-DEFB1 expression ratio based on the expression levels of PAX2 and DEFB1.   
     
     
         5 . The method of  claim 4 , wherein the expression levels of PAX2, DEFB1 and the control genes are determined by quantitative real-time RT-PCR. 
     
     
         6 . The method of  claim 4 , wherein the expression levels of PAX2, DEFB1 and the control genes are determined by expression microarray. 
     
     
         7 . The method of  claim 4 , wherein the control gene is the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. 
     
     
         8 . The method of  claim 1 , further comprising determining an oestrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (ER/PR/HER2) status in cells obtained from the breast tissue. 
     
     
         9 . A kit for monitoring breast conditions in a subject, comprising:
 one or more pairs of oligonucleotide primers for detecting PAX2 expression in a tissue sample;   one or more pairs of oligonucleotide primers for detecting DEFB1 expression in the tissue sample; and   instructions on how to determine the PAX2-to-DEFB1 expression ratio in a tissue sample using the primers.   
     
     
         10 . The kit of  claim 9 , wherein the one or more pairs of oligonucleotide primers for detecting PAX2 expression comprising an oligonucleotide primer pair selected from the group consisting of SEQ ID NOS: 43 and 47, SEQ ID NOS: 44 and 48, and SEQ ID NOS: 45 and 49. 
     
     
         11 . The kit of  claim 9 , wherein the one or more pairs of oligonucleotide primers for detecting DEFB1 expression comprising SEQ ID NOS: 35 and 37. 
     
     
         12 . The kit of  claim 9 , further comprising one or more pairs of control oligonucleotide primers. 
     
     
         13 . The kit of  claim 12 , wherein the one or more pairs of control oligonucleotide primers comprise oligonucleotide primers for detecting expression of β-actin expression. 
     
     
         14 . The kit of  claim 13 , wherein the oligonucleotide primers for detecting expression of β-actin expression comprise SEQ ID NOS: 34 and 36. 
     
     
         15 . The kit of  claim 12 , wherein the one or more pairs of control oligonucleotide primers comprise oligonucleotide primers for detecting expression of GAPDH expression. 
     
     
         16 . The kit of  claim 15 , wherein the oligonucleotide primers for detecting expression of GAPDH expression comprise SEQ JD NOS: 42 and 46. 
     
     
         17 . The kit of  claim 9 , further comprising one or more reagents for PCR reaction. 
     
     
         18 . The kit of  claim 9 , further comprising one or more reagents for RNA extraction. 
     
     
         19 . A kit for monitoring breast conditions in a subject, comprising:
 an oligonucleotide microarray having oligonucleotide probes for detecting PAX2 and DEFB1 expression; and   instructions on how to determine the PAX2-to-DEFB1 expression ratio in a tissue sample using the oligonucleotide microarray.   
     
     
         20 . The kit of  claim 19 , further comprising reagents for extracting RNA from a tissue sample. 
     
     
         21 . A method for determining a treatment regimen for a subject with a breast condition, comprising:
 determining the expression level of PAX2 gene relative to the expression level of a control gene in cells obtained from a breast tissue with the breast condition in said subject; and   determining a treatment regimen for said subject based on the relative expression level of the PAX2 gene.   
     
     
         22 . The method of  claim 21 , wherein said control gene is actin gene or GAPDH gene. 
     
     
         23 . The method of  claim 21 , wherein said breast condition is oestrogen receptor negative and/or, progesterone receptor negative and/or human epidermal growth factor receptor 2 negative breast cancer. 
     
     
         24 . The method of  claim 21 , wherein said breast condition is oestrogen receptor positive and/or, progesterone receptor positive, and/or human epidermal growth factor receptor 2 positive breast cancer.