Biomarkers for gastric cancer and uses thereof

Abstract

The present invention provides biological markers associated with gastric cancer. In particular, the present invention provides a method of diagnosing gastric cancer (GC) in a subject, the method including: measuring an expression level of one or more proteins in the subject, wherein the one or more proteins are selected from the group consisting of vitamin D binding protein (VDBP), clusterin, insulin like growth factor binding protein complex acid labile subunit (IGFALS), and afamin; comparing the expression level of the or each protein in the subject to a reference expression level for the or each protein; and diagnosing GC in the subject on the basis of the comparison. On the basis of the identification of biological markers associated with gastric cancer, the present invention also provides a method of determining if a subject is susceptible to developing gastric cancer, a method of assessing progression of gastric cancer in a subject, a method for screening a candidate therapeutic agent useful for treating gastric cancer in a subject, and a kit for diagnosing gastric cancer in a subject.

1 . A method of diagnosing gastric cancer (GC) in a subject, the method including:
 (a) measuring an expression level of one or more biomarkers in the subject, wherein the one or more biomarkers are selected from the group consisting of vitamin D binding protein (VDBP), clusterin, insulin like growth factor binding protein complex acid labile subunit (IGFALS), and afamin;   (b) comparing the expression level of the or each biomarker in the subject to a reference expression level for the or each biomarker; and   (c) diagnosing GC in the subject on the basis of the comparison.   
     
     
         2 . The method according to  claim 1 , wherein the expression level of the one or more biomarkers is measured in a sample obtained from the subject. 
     
     
         3 . The method according to  claim 2 , wherein the sample is a serum sample. 
     
     
         4 . The method according to  claim 3 , wherein measuring the expression level of the one or more biomarkers includes measuring the level of biomarker protein in the sample. 
     
     
         5 . The method according to  claim 2 , wherein the sample is a tissue sample. 
     
     
         6 . The method according to  claim 5 , wherein measuring the expression level of the one or more biomarkers includes measuring the level of biomarker mRNA in the sample. 
     
     
         7 . The method according to any one of  claims 1  to  6 , wherein the biomarker is human VDBP. 
     
     
         8 . The method according to  claim 7 , wherein an expression level of VDBP in the subject that is lower than the reference expression level for VDBP is indicative of GC in the subject. 
     
     
         9 . The method according to any one of  claims 1  to  6 , wherein the biomarker is human clusterin. 
     
     
         10 . The method according to  claim 9 , wherein an expression level of clusterin in the subject that is lower than the reference expression level for clusterin is indicative of GC in the subject. 
     
     
         11 . The method according to any one of  claims 1  to  6 , wherein the biomarker is human IGFALS. 
     
     
         12 . The method according to  claim 11 , wherein an expression level of IGFALS in the subject that is higher than the reference expression level for IGFALS is indicative of GC in the subject. 
     
     
         13 . The method according to any one of  claims 1  to  6 , wherein the biomarker is human afamin. 
     
     
         14 . The method according to  claim 13 , wherein an expression level of afamin in the subject that is lower than the reference expression level for afamin is indicative of GC in the subject. 
     
     
         15 . A method of determining if a subject is susceptible to developing gastric cancer (GC), the method including:
 (a) measuring an expression level of one or more biomarkers in the subject, wherein the one or more biomarkers are selected from the group consisting of vitamin D binding protein (VDBP), clusterin, insulin like growth factor binding protein complex acid labile subunit (IGFALS), and afamin;   (b) comparing the expression level of the or each biomarker in the subject to a reference expression level for the or each biomarker; and   (c) determining if the subject is susceptible to developing GC on the basis of the comparison.   
     
     
         16 . The method according to  claim 15 , wherein the expression level of the one or more biomarkers is measured in a sample obtained from the subject. 
     
     
         17 . The method according to  claim 16 , wherein the sample is a serum sample. 
     
     
         18 . The method according to  claim 17 , wherein measuring the expression level of the one or more biomarkers includes measuring the level of biomarker protein in the sample. 
     
     
         19 . The method according to  claim 16 , wherein the sample is a tissue sample. 
     
     
         20 . The method according to  claim 19 , wherein measuring the expression level of the one or more biomarkers includes measuring the level of biomarker mRNA in the sample. 
     
     
         21 . The method according to any one of  claims 15  to  20 , wherein the biomarker is human VDBP. 
     
     
         22 . The method according to  claim 21 , wherein an expression level of VDBP in the subject that is lower than the reference expression level for VDBP is indicative of GC in the subject. 
     
     
         23 . The method according to any one of  claims 15  to  20 , wherein the biomarker is human clusterin. 
     
     
         24 . The method according to  claim 23 , wherein an expression level of clusterin in the subject that is lower than the reference expression level for clusterin is indicative of GC in the subject. 
     
     
         25 . The method according to any one of  claims 15  to  20 , wherein the biomarker is human IGFALS. 
     
     
         26 . The method according to  claim 25 , wherein an expression level of IGFALS in the subject that is higher than the reference expression level for IGFALS is indicative of GC in the subject. 
     
     
         27 . The method according to any one of  claims 15  to  20 , wherein the biomarker is human afamin. 
     
     
         28 . The method according to  claim 27 , wherein an expression level of afamin in the subject that is lower than the reference expression level for afamin is indicative of GC in the subject. 
     
     
         29 . A method of assessing progression of gastric cancer (GC) in a subject, the method including:
 (a) measuring an expression level of one or more biomarkers in the subject, wherein the one or more biomarkers are selected from the group consisting of vitamin D binding protein (VDBP), clusterin, insulin like growth factor binding protein complex acid labile subunit (IGFALS), and afamin;   (b) comparing the expression level of the or each biomarker in the subject to a reference expression level for the or each biomarker; and   (c) assessing the progression of GC in the subject on the basis of the comparison.   
     
     
         30 . The method according to  claim 29 , wherein the subject is undergoing treatment for the GC. 
     
     
         31 . The method according to  claim 29  or  claim 30 , wherein the expression level of the one or more biomarkers is measured in a sample obtained from the subject. 
     
     
         32 . The method according to  claim 31 , wherein the sample is a serum sample. 
     
     
         33 . The method according to  claim 32 , wherein measuring the expression level of the one or more biomarkers includes measuring the level of biomarker protein in the sample. 
     
     
         34 . The method according to  claim 31 , wherein the sample is a tissue sample. 
     
     
         35 . The method according to  claim 34 , wherein measuring the expression level of the one or more biomarkers includes measuring the level of biomarker mRNA in the sample. 
     
     
         36 . The method according to any one of  claims 29  to  35 , wherein the biomarker is human VDBP. 
     
     
         37 . The method according to  claim 36 , wherein an expression level of VDBP in the subject that is lower than the reference expression level for VDBP is indicative of GC in the subject. 
     
     
         38 . The method according to any one of  claims 29  to  35 , wherein the biomarker is human clusterin. 
     
     
         39 . The method according to  claim 38 , wherein an expression level of clusterin in the subject that is lower than the reference expression level for clusterin is indicative of GC in the subject. 
     
     
         40 . The method according to any one of  claims 29  to  35 , wherein the biomarker is human IGFALS. 
     
     
         41 . The method according to  claim 40 , wherein an expression level of IGFALS in the subject that is higher than the reference expression level for IGFALS is indicative of GC in the subject. 
     
     
         42 . The method according to any one of  claims 29  to  35 , wherein the biomarker is human afamin. 
     
     
         43 . The method according to  claim 42 , wherein an expression level of afamin in the subject that is lower than the reference expression level for afamin is indicative of GC in the subject. 
     
     
         44 . A method for screening a candidate therapeutic agent useful for treating gastric cancer (GC) in a subject, the method including assaying the candidate therapeutic agent for activity in modulating the expression level of one or more biomarkers selected from the group consisting of vitamin D binding protein (VDBP), clusterin, insulin like growth factor binding protein complex acid labile subunit (IGFALS), and afamin. 
     
     
         45 . The method according to  claim 44 , the method including:
 (a) administering the candidate therapeutic agent to the subject;   (b) measuring the expression level of the or each biomarker in the subject; and   (c) comparing the expression level of the or each biomarker in the subject to a reference expression level for the or each biomarker,   wherein if the expression level of the or each biomarker approximates or is identical to the reference expression level for the or each biomarker, the candidate therapeutic agent is useful for treating GC in the subject.   
     
     
         46 . The method according to  claim 44 , the method including:
 (a) exposing the candidate therapeutic agent to a cell expressing the or each biomarker;   (b) measuring for a change in the expression level of the or each biomarker in the cell; and   (c) comparing the expression level of the or each biomarker in the subject to a reference expression level for the or each biomarker,   wherein if the expression level of the or each biomarker approximates or is identical to the reference expression level for the or each biomarker, the candidate therapeutic agent is useful for treating GC in a subject.   
     
     
         47 . The method according to  claim 45  or  claim 46 , wherein the candidate therapeutic agent increases the expression level of VDBP in the subject or cell to a level which approximates or is identical to the reference expression level for VDBP. 
     
     
         48 . The method according to  claim 45  or  claim 46 , wherein the candidate therapeutic agent increases the expression level of clusterin in the subject or cell to a level which approximates or is identical to the reference expression level for clusterin. 
     
     
         49 . The method according to  claim 45  or  claim 46 , wherein the candidate therapeutic agent decreases the expression level of IGFALS in the subject or cell to a level which approximates or is identical to the reference expression level for IGFALS. 
     
     
         50 . The method according to  claim 45  or  claim 46 , wherein the candidate therapeutic agent increases the expression level of afamin in the subject or cell to a level which approximates or is identical to the reference expression level for afamin. 
     
     
         51 . The method according to any one of  claims 1  to  50 , wherein the method further includes measuring an expression level of the biomarker apolipoprotein E (ApoE) and/or the biomarker haptoglobin in the subject or cell. 
     
     
         52 . A kit for diagnosing gastric cancer (GC) in a subject, determining if a subject is susceptible to developing GC, or assessing progression of GC in a subject, the kit including means for measuring an expression level of one or more biomarkers in the subject, wherein the one or more biomarkers are selected from the group consisting of vitamin D binding protein (VDBP), clusterin, insulin like growth factor binding protein complex acid labile subunit (IGFALS), and afamin.