Esophageal Cancer Markers

Abstract

The present invention is directed to methods for diagnosing cancer in a subject. Morphologically normal epithelial cells of the esophagus are assayed for marker expression. Characteristic expression of the markers indicates the presence of cancer or the predisposition to cancer. A panel of eleven markers are particularly good at identifying cancer and the predisposition to cancer.

1 . A method of determining presence or predisposition to esophageal cancer in a human subject, comprising:
 determining in a sample of morphologically normal esophageal epithelial cells of a human subject expression of one or more genes;   determining a composite score of expression of the one or more genes;   comparing the composite score to predetermined values for esophageal cancer or predisposition to esophageal cancer;   identifying presence or predisposition to esophageal cancer based on the composite score.   
     
     
         2 . A method of determining presence or predisposition to esophageal cancer in a human subject, comprising:
 determining in a sample of esophageal epithelial cells of a human subject expression of one or more genes selected from the group consisting of gravin; H1 histone family, member 2 (H1F2); H2A histone family, member L (H2AFL); H2B histone family, member C (H2BFC); keratin 8 (KRT8); progestin induced protein (DD5); H2A histone family, member 0 (H2AFO); transglutaminase 3 (TGF3); major histocopatibility complex, class II, DR alpha (HLA-DRA); mitotic checkpoint protein kinase BUB1B (BUB1B); and glutathione peroxidase 2 (gastrointestinal) (GPX2);   determining a composite score of expression of the one or more genes;   comparing the composite score to predetermined values for esophageal cancer or predisposition to esophageal cancer;   identifying presence or predisposition to esophageal cancer based on the composite score.   
     
     
         3 . The method of  claim 2  wherein the sample comprises morphologically normal esophageal epithelial cells. 
     
     
         4 . The method of  claim 1  wherein mRNA expression of the one or more genes is determined. 
     
     
         5 . The method of  claim 1  wherein protein expression of the one or more genes is determined. 
     
     
         6 . The method of  claim 2  wherein a composite score of expression of eleven genes is determined. 
     
     
         7 . The method of  claim 2  wherein a composite score of expression of ten genes is determined. 
     
     
         8 . The method of  claim 2  wherein a composite score of expression of nine genes is determined. 
     
     
         9 . The method of  claim 2  wherein a composite score of expression of eight genes is determined. 
     
     
         10 . The method of  claim 2  wherein a composite score of expression of seven genes is determined. 
     
     
         11 . The method of  claim 2  wherein a composite score of expression of six genes is determined. 
     
     
         12 . The method of  claim 2  wherein a composite score of expression of five genes is determined. 
     
     
         13 . The method of  claim 1  wherein a chemopreventive diet is recommended when presence or predisposition to esophageal cancer is identified. 
     
     
         14 . The method of  claim 1  wherein the sample is obtained by endoscopy. 
     
     
         15 . The method of  claim 1  wherein the sample is obtained by an inflatable balloon. 
     
     
         16 . The method of  claim 1  wherein the sample is obtained by a sponge. 
     
     
         17 . The method of  claim 1  wherein the human subject has diagnosed Barrett's esophagus. 
     
     
         18 . A solid support for determining esophageal epithelium expression, comprising: antibodies or oligonucleotide probes for interrogating expression of at least six genes selected from the group consisting of gravin; H1 histone family, member 2 (H1F2); H2A histone family, member L (H2AFL); H2B histone family, member C (H2BFC); keratin 8 (KRT8); progestin induced protein (DD5); H2A histone family, member O (H2AFO); transglutaminase 3 (TGF3); major histocompatibility complex, class II, DR alpha (HLA-DRA); mitotic checkpoint protein kinase BUB1B (BUB1B); and glutathione peroxidase 2 (gastrointestinal) (GPX2); wherein the antibodies or oligonucleotide probes for the at least six genes from the group comprise at least 50% of the antibodies or oligonucleotide probes on the solid support. 
     
     
         19 . The solid support of  claim 18  wherein the antibodies or oligonucleotide probes for the at least six genes from the group comprise at least 75% of the antibodies or oligonucleotide probes on the solid support. 
     
     
         20 . The solid support of  claim 18  wherein the antibodies or oligonucleotide probes for the at least six genes from the group comprise at least 90% of the antibodies or oligonucleotide probes on the solid support.