Glycoprotein cancer biomarker

Abstract

The invention relates to glycoproteins having a cancer-specific glycoform. Cancer-specific glycoforms are useful in diagnostics and therapeutics.

1 . A method for evaluating the presence, absence, nature or extent of ovarian cancer or a precancerous condition of the ovary, the method comprising:
 providing a biological sample obtained from a subject, the biological sample comprising glycoproteins;   contacting the biological sample with a glycan-binding molecule specific for a glycan, under conditions that permit binding of the glycan-binding molecule to a glycoprotein comprising said glycan;   detecting binding of the glycan-binding molecule to the glycoprotein to determine the presence, absence or amount of a cancer-specific glycoform of the glycoprotein in the biological sample, wherein said cancer-specific glycoform comprises the glycan and is indicative of ovarian cancer or a precancerous condition of the ovary;   wherein the plurality of glycoproteins are selected from the group consisting of periostin (POSTN), biglycan (BGN), heparan sulfate proteoglycan 2 (HSPG2), lactate dehydrogenase A (LDHA), thrombospondin 1 (THBS1) serine protease inhibitor H1 (SERPINH1), lysosomal-associated membrane glycoprotein 1 (LAMP1), lectin galactosidase soluble binding protein 3 (LGALS3BP), complement factor B (CFB), fibulin 5 (FBLN5), mucin 5b (MUC5b), and lactotransferrin (LTF); and   wherein the presence, absence or amount of the cancer-specific glycoform is indicative of the presence, absence, nature or extent of ovarian cancer or a precancerous condition of the ovary.   
     
     
         2 . The method of  claim 1  wherein the glycan-binding molecule comprises a detectable label. 
     
     
         3 . The method of  claim 1  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. 
     
     
         4 . The method of  claim 1  wherein the lectin comprises at least one lectin selected from the group consisting of erythroagglutinating phytohemagglutinin (E-PHA),  Aleuria aurantia  lectin (AAL) and  Datura stramonium  lectin (DSL). 
     
     
         5 . The method of  claim 1  wherein the glycan comprises an α(1,6)-fucose linked to core N-acetylglucosamine (core fucosylation). 
     
     
         6 . The method of  claim 1  wherein the glycan comprises a GlcNAc β(1,4) Man bisected N-linked glycan. 
     
     
         7 . The method of  claim 1  wherein the biological sample comprises a biological fluid. 
     
     
         8 . The method of  claim 1  wherein the biological sample comprises serum or plasma. 
     
     
         9 . The method of  claim 1  wherein the biological sample comprises tissue. 
     
     
         10 . The method of  claim 1  wherein the subject is a human. 
     
     
         11 . The method of  claim 1  wherein the glycan comprises a bisecting N-linked glycan. 
     
     
         12 . The method of  claim 1  wherein the glycan comprises core fucosylation. 
     
     
         13 . The method of  claim 1  wherein the glycan comprises a tri- or tetra-antennary complex N-linked glycan. 
     
     
         14 . The method of  claim 1  wherein the glycan comprises a β(1,4) branched glycan. 
     
     
         15 . A method for evaluating the presence, absence, nature or extent of ovarian cancer or a precancerous condition of the ovary, the method comprising:
 contacting a biological sample obtained from a subject, with a glycan-binding molecule specific for a glycan under conditions that permit binding of the glycan-binding molecule to a glycoprotein comprising said glycan; and   detecting binding of the glycan-binding molecule to the glycoprotein to determine the presence of a cancer-specific glycoform of the glycoprotein in the biological sample, wherein the cancer-specific glycoform comprises the glycan and is indicative of the presence of cancer or a precancerous condition of the ovary; and wherein the glycoprotein is selected from the group consisting of periostin (POSTN), biglycan (BGN), heparan sulfate proteoglycan 2 (HSPG2), lactate dehydrogenase A (LDHA), thrombospondin 1 (THBS1) serine protease inhibitor H1 (SERPINH1), lysosomal-associated membrane glycoprotein 1 (LAMP1), lectin galactosidase soluble binding protein 3 (LGALS3BP), complement factor B (CFB), fibulin 5 (FBLN5), mucin 5b (MUC5b), and lactotransferrin (LTF).   
     
     
         16 . A diagnostic composition comprising a biomarker comprising a cancer-specific glycoform of periostin comprising a bisected N-linked glycan component or core fucosylation. 
     
     
         17 . A diagnostic composition comprising a biomarker comprising a isolated cancer-specific glycoform of thrombospondin 1 (THBS1) comprising core fucosylation. 
     
     
         18 . A diagnostic composition comprising a biomarker comprising a cancer-specific glycoform of lysosomal-associated membrane glycoprotein 1 (LAMP1) comprising core fucosylation or a tri- or tetra-antennary complex N-linked glycan.