Glycoprotein biomarkers for esophageal adenocarcinoma and barrett's esophagus and uses thereof

Abstract

Disclosed are biomarkers for Barrett's esophagus and esophageal adenocarcinoma, and uses thereof, such as in methods for detecting the presence, and monitoring progression, of Barrett's esophagus and esophageal adenocarcinoma. Also disclosed are methods for treating and methods of monitoring the treatment of Barrett's esophagus and esophageal adenocarcinoma, as well as kits and compositions for use in such methods.

1 .- 54 . (canceled) 
     
     
         55 . A composition comprising a biological sample from a subject having or suspected of having Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) comprising a glycospecies of at least one glycoprotein; and one or more reagents for determining the level of said glycospecies, wherein the at least one glycoprotein comprises complement C9. 
     
     
         56 . The composition of  claim 55 , wherein the composition comprises a glycospecies of at least one other glycoprotein selected from the group consisting of gelsolin, N-acetylmuramoyl-L-alanine amidase, afamin, alpha-1-antichymotrypsin, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS -glycoprotein, alpha-2-macroglobulin, apolipoprotein B-100, beta-2-glycoprotein 1, ceruloplasmin, complement C1q subcomponent subunit B, complement C4b-binding protein alpha chain, complement C5, complement C7, complement factor B, haptoglobin, hemopexin, kallistatin, plasma kallikrein, plasma protease C 1 inhibitor, serum paraoxonase/arylesterase 1, serum paraoxonase/lactonase 3, retinol-binding protein 4, complement C4b-binding protein beta chain and serotransferrin; and a reagent for determining the level of said glycospecies. 
     
     
         57 . The composition of  claim 56 , wherein the at least one other glycoprotein comprises gelsolin. 
     
     
         58 . The composition of  claim 55 , wherein the one or more reagents comprise an antibody. 
     
     
         59 . The composition of  claim 55 , wherein the one or more reagents comprise a glycan-binding molecule. 
     
     
         60 . The composition of  claim 59 , wherein the glycan-binding molecule is selected from the group consisting of a lectin, a glycospecific antibody, a glycospecific aptamer, a glycospecific peptide and a glycospecific small molecule. 
     
     
         61 . The composition of  claim 59 , wherein the glycan-binding molecule is a lectin selected from the group consisting of Aleuria aurantia lectin (AAL), Pisum sativum agglutinin (PSA), erythroagglutinating phytohemagglutinin (EPHA), jacalin (JAC), Narcissus pseudonarcissus lectin (NPL) and wheat germ agglutinin (WGA). 
     
     
         62 . The composition of  claim 55 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds are selected from the group consisting of AAL:complement C9, AAL:gelsolin, AAL:N-acetylmuramoyl-L-alanine amidase, AAL:retinol-binding protein 4, PSA:haptoglobulin, PSA:complement C9, PSA:gelsolin, EPHA:haptoglobin, EPHA:complement factor B, EPHA:complement C9, EPHA:gelsolin, EPHA:alpha-2-macroglobulin, EPHA:alpha-2-HS -glycoprotein, EPHA:N-acetylmuramoyl-L-alanine amidase, EPHA: serum paraoxonase/lactonase 3, JAC:alpha-l-antitrypsin, JAC:ceruloplasmin, JAC:complement factor B, JAC:alpha-1-antichymotrypsin, JAC:complement C5, JAC:complement C9, JAC:hemopexin, JAC:C4b-binding protein alpha chain, JAC:N-acetylmuramoyl-L-alanine amidase, JAC:plasma kallikrein, JAC:plasma protease C 1 inhibitor, JAC:heparin cofactor 2, JAC:gelsolin, NPL:ceruloplasmin, NPL:gelsolin, NPL:haptoglobin, NPL:alpha-1-antichymotrypsin, NPL:complement C9, NPL:C4b-binding protein alpha chain, NPL:N-acetylmuramoyl-L-alanine amidase, NPL: serum paraoxonase/arylesterase 1, NPL: serum paraoxonase/lactonase 3, WGA:haptoglobin, WGA:alpha-1-antichymotrypsin, WGA:complement C1q subcomponent subunit B and WGA:complement C9. 
     
     
         63 . The composition of  claim 55 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds are selected from the group consisting of AAL:haptoglobin, AAL:complement C5, AAL:complement C9, AAL:complement C7, AAL:apolipoprotein B-100, AAL:gelsolin, AAL:retinol-binding protein 4, PSA:haptoglobin, PSA:alpha-l-antichymotrypsin, PSA:complement 5, PSA:complement C9, PSA:complement C7, PSA:gelsolin, EPHA:haptoglobin, EPHA:alpha-1-antichymotrypsin, EPHA:complement C9, EPHA:serotransferrin, EPHA:complement factor B, EPHA:complement C7, EPHA:gelsolin, EPHA:serum paraoxonase/lactonase 3, JAC:haptoglobin, JAC:complement factor B, JAC:alpha-1-antitrypsin, JAC: alpha-1-antichymotrypsin, JAC:ceruploplasmin, JAC:complement C5, JAC:complement C9, JAC:alpha-1B-glycoprotein, JAC:complement C7, JAC:gelsolin, NPL:complement C9, NPL: apolipoprotein B-100, NPL:gelsolin, NPL:afamin, WGA:haptoglobin, WGA:complement C9 and WGA:gelsolin. 
     
     
         64 . The composition of  claim 56 , wherein the at least one other glycoprotein is selected from the group consisting of gelsolin, alpha-1-antitrypsin, serum paraoxonase/arylesterase 1, serum paraoxonase/lactonase 3 and plasma kallikrein. 
     
     
         65 . The composition of  claim 64 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds, are selected from the group consisting of JAC:complement C9, NPL:complement C9, EPHA:complement C9, EPHA:gelsolin, JAC:gelsolin, NPL:gelsolin, NPL:serum paraoxonase/arylesterase 1, NPL: serum paraoxonase/lactonase 3, EPHA:serum paraoxonase/lactonase 3, JAC:alpha-1-antitrypsin and JAC:plasma kallikrein. 
     
     
         66 . The composition of  claim 57 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds are selected from the group consisting of AAL:complement C9, AAL:gelsolin, PSA:complement C9, PSA:gelsolin, EPHA:complement C9, EPHA:gelsolin, JAC:complement C9, JAC:gelsolin, NPL:complement C9 and WGA:complement C9. 
     
     
         67 . The composition of  claim 57 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds are selected from the group consisting of AAL:complement C9, AAL:gelsolin, PSA:complement C9, PSA:gelsolin, EPHA:complement C9, EPHA:gelsolin, JAC:complement C9, JAC:gelsolin, NPL:complement C9, NPL:gelsolin, WGA:complement C9 and WGA:gelsolin. 
     
     
         68 . The composition of  claim 55 , wherein the biological sample is a serum, plasma or blood sample. 
     
     
         69 . A method of treating esophageal adenocarcinoma (EAC) in a subject, comprising:
 a) determining in a sample from the subject the level of a glycospecies of at least one glycoprotein, which glycospecies is differentially expressed between EAC and one or more other conditions selected from healthy condition (HC) and Barrett's esophagus (BE), and determining a likelihood of the subject having EAC based on whether the respective levels of the individual glycospecies are above or below a corresponding predetermined threshold that correlates with the presence of EAC, wherein the at least one glycoprotein comprises complement C9; and   b) exposing the subject to a treatment regimen for EAC.   
     
     
         70 . The method of  claim 69 , wherein the method further comprises determining the level of a glycospecies of at least one other glycoprotein selected from the group consisting of gelsolin, N-acetylmuramoyl-L-alanine amidase, afamin, alpha-1-antichymotrypsin, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS -glycoprotein, alpha-2-macroglobulin, apolipoprotein B-100, beta-2-glycoprotein 1, ceruloplasmin, complement C1q subcomponent subunit B, complement C4b-binding protein alpha chain, complement C5, complement C7, complement factor B, haptoglobin, hemopexin, kallistatin, plasma kallikrein, plasma protease C1 inhibitor, serum paraoxonase/arylesterase 1, serum paraoxonase/lactonase 3, retinol-binding protein 4, complement C4b-binding protein beta chain and serotransferrin. 
     
     
         71 . The method of  claim 70 , wherein the at least one other glycoprotein comprises gelsolin. 
     
     
         72 . The method of  claim 69 , wherein the level of an individual glycospecies is determined by contacting the sample with a glycan-binding molecule under conditions that permit binding of the glycan-binding molecule to the glycospecies. 
     
     
         73 . The method of  claim 72 , wherein the glycan-binding molecule is selected from the group consisting of a lectin, a glycospecific antibody, a glycospecific aptamer, a glycospecific peptide and a glycospecific small molecule. 
     
     
         74 . The method of  claim 73 , wherein the glycan-binding molecule is a lectin selected from the group consisting of Aleuria aurantia lectin (AAL), Pisum sativum agglutinin (PSA), erythroagglutinating phytohemagglutinin (EPHA), jacalin (JAC), Narcissus pseudonarcissus lectin (NPL) and wheat germ agglutinin (WGA). 
     
     
         75 . The method of  claim 74 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds and which are differentially expressed between EAC and HC are selected from the group consisting of AAL:complement C9, AAL:gelsolin, AAL:N-acetylmuramoyl-L-alanine amidase, AAL:retinol-binding protein 4, PSA:haptoglobulin, PSA:complement C9, PSA:gelsolin, EPHA:haptoglobin, EPHA:complement factor B, EPHA:complement C9, EPHA:gelsolin, EPHA:alpha-2-macroglobulin, EPHA:alpha-2-HS-glycoprotein, EPHA:N-acetylmuramoyl-L-alanine amidase, EPHA: serum paraoxonase/lactonase 3, JAC:alpha-1-antitrypsin, JAC: ceruloplasmin, JAC:complement factor B, JAC:alpha-1-antichymotrypsin, JAC:complement C5, JAC:complement C9, JAC:hemopexin, JAC:C4b-binding protein alpha chain, JAC:N-acetylmuramoyl-L-alanine amidase, JAC:plasma kallikrein, JAC:plasma protease C 1  inhibitor, JAC:heparin cofactor 2, JAC:gelsolin, NPL:ceruloplasmin, NPL:gelsolin, NPL:haptoglobin, NPL: alpha-1-antichymotrypsin, NPL:complement C9, NPL:C4b-binding protein alpha chain, NPL:N-acetylmuramoyl-L-alanine amidase, NPL: serum paraoxonase/arylesterase 1, NPL: serum paraoxonase/lactonase 3, WGA:haptoglobin, WGA:alpha-1-antichymotrypsin, WGA:complement C1q subcomponent subunit B and WGA:complement C9. 
     
     
         76 . The method of  claim 74 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds and which are differentially expressed between EAC and BE are selected from the group consisting of AAL:haptoglobin, AAL:complement C5, AAL:complement C9, AAL:complement C7, AAL:apolipoprotein B-100, AAL:gelsolin, AAL:retinol-binding protein 4, PSA:haptoglobin, PSA:alpha-1-antichymotrypsin, PSA:complement 5, PSA:complement C9, PSA:complement C7, PSA:gelsolin, EPHA:haptoglobin, EPHA: alpha-1-antichymotrypsin, EPHA:complement C9, EPHA:serotransferrin, EPHA:complement factor B, EPHA:complement C7, EPHA:gelsolin, EPHA:serum paraoxonase/lactonase 3, JAC:haptoglobin, JAC:complement factor B, JAC:alpha-1-antitrypsin, JAC: alpha-1-antichymotrypsin, JAC:ceruploplasmin, JAC:complement C5, JAC:complement C9, JAC:alpha-1B-glycoprotein, JAC:complement C7, JAC:gelsolin, NPL:complement C9, NPL: apolipoprotein B-100, NPL:gelsolin, NPL:afamin, WGA:haptoglobin, WGA:complement C9 and WGA:gelsolin. 
     
     
         77 . The method of  claim 70 , wherein the at least one other glycoprotein is selected from the group consisting of gelsolin, alpha-1-antitrypsin, serum paraoxonase/arylesterase 1, serum paraoxonase/lactonase 3 and plasma kallikrein. 
     
     
         78 . The method of  claim 77 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds, are selected from the group consisting of JAC:complement C9, NPL:complement C9, EPHA:complement C9, EPHA:gelsolin, JAC:gelsolin, NPL:gelsolin, NPL:serum paraoxonase/arylesterase 1, NPL: serum paraoxonase/lactonase 3, EPHA:serum paraoxonase/lactonase 3, JAC:alpha-1-antitrypsin and JAC:plasma kallikrein. 
     
     
         79 . The method of  claim 71 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds and which are differentially expressed between EAC and HC are selected from the group consisting of AAL:complement C9, AAL:gelsolin, PSA:complement C9, PSA:gelsolin, EPHA:complement C9, EPHA:gelsolin, JAC:complement C9, JAC:gelsolin, NPL:complement C9 and WGA:complement C9. 
     
     
         80 . The method of  claim 71 , wherein individual glycospecies defined by a glycan-binding molecule and the glycoprotein to which it binds and which are differentially expressed between EAC and BE are selected from the group consisting of AAL:complement C9, AAL:gelsolin, PSA:complement C9, PSA:gelsolin, EPHA:complement C9, EPHA:gelsolin, JAC:complement C9, JAC:gelsolin, NPL:complement C9, NPL:gelsolin, WGA:complement C9 and WGA:gelsolin. 
     
     
         81 . The method of  claim 69 , wherein the treatment regimen comprises surgery, radiotherapy or chemotherapy. 
     
     
         82 . The method of  claim 81 , wherein the treatment regimen comprises surgery, and said surgery removes all or part of the esophagus.