Podxl protein in colorectal cancer

Abstract

The present disclosure provides a method for determining whether a mammalian subject having a colorectal cancer belongs to a first or a second group, wherein the prognosis of subjects of the first group is better than the prognosis of subjects of the second group, comprising the steps of: a) evaluating an amount of PODXL protein in at least part of a sample earlier obtained from the subject, and determining a sample value corresponding to the evaluated amount; b) comparing said sample value from step a) with a predetermined reference value; and if said sample value is higher than said reference value, c1) concluding that the subject belongs to said second group; and if said sample value is lower than or equal to said reference value, c2) concluding that the subject belongs to said first group. Related uses, means and a method of treatment are also provided.

1 . Method of treatment of a subject having a colorectal cancer, comprising:
 a) evaluating an amount of PODXL protein present in at least part of a sample from the subject and determining a sample value corresponding to the evaluated amount;   b) comparing the sample value obtained in step a) with a reference value; and, if said sample value is higher than said reference value,   c) treating said subject with a colorectal cancer treatment regimen.   
     
     
         2 . Method for determining whether a mammalian subject having a colorectal cancer belongs to a first or a second group, wherein the prognosis of subjects of the first group is better than the prognosis of subjects of the second group, comprising the steps of:
 a) evaluating an amount of PODXL protein in at least part of a sample earlier obtained from the subject, and determining a sample value corresponding to the evaluated amount;   b) comparing said sample value from step a) with a predetermined reference value; and
 if said sample value is higher than said reference value, 
   c1) concluding that the subject belongs to said second group; and
 if said sample value is lower than or equal to said reference value, 
   c2) concluding that the subject belongs to said first group.   
     
     
         3 . Method according to  claim 2 , wherein each of the first and the second group has two subgroups, α and β, and the prognosis of subjects of the subgroup α is better than the prognosis of subjects of the subgroup β in each of the first and the second group, the method further comprising the steps of:
 d) evaluating an amount of COX-2 protein in at least part of a sample earlier obtained from the subject, and determining a sample value corresponding to the evaluated amount; 
 e) comparing said sample value from step d) with a predetermined reference value; and
 if the sample value from step d) is higher than the reference value of step e), 
 
 f1) concluding that the subject belongs to subgroup β; and
 if the sample value from step d) is lower than or equal to the reference value of step e), 
 
 f2) concluding that the subject belongs to subgroup α. 
 
     
     
         4 . Non-treatment strategy method for a subject having a colorectal cancer, comprising:
 a) evaluating an amount of PODXL protein present in at least part of a sample earlier obtained from the subject, and determining a sample value corresponding to the evaluated amount;   b) comparing the sample value obtained in step a) with a reference value; and,
 if said sample value is lower than or equal to said reference value, 
   c) refraining from treating said subject with a colorectal cancer treatment regimen.   
     
     
         5 . Method according to  claim 1 , wherein the colorectal cancer is in Dukes' stage B or TNM stage II. 
     
     
         6 . Method according to  claim 5 , wherein the colorectal cancer treatment regimen is an adjuvant colorectal cancer chemotherapy. 
     
     
         7 . Method according to  claim 6 , further comprising:
 d) refraining from treating the subject with the adjuvant colorectal treatment regimen if said sample value is lower than or equal to said reference value.   
     
     
         8 . Method according to  claim 1 , wherein the colorectal cancer is in Dukes' stage C or TNM stage III. 
     
     
         9 . Method according to  claim 8 , wherein the colorectal cancer treatment regimen comprises the administration of a combination of two or more chemotherapeutic agents. 
     
     
         10 . Method according to  claim 9 , further comprising:
 d) wherein the colorectal cancer treatment regimen comprises the administration of a single chemotherapeutic agent if said sample value is lower than or equal to said reference value.   
     
     
         11 . Method according to  claim 1 , wherein the evaluation of step a) is limited to the membranes of tumor cells of said sample. 
     
     
         12 . Method according to  claim 1 , wherein the evaluation of step a) is limited to the membranes of tumor budding cells of said sample. 
     
     
         13 . Method according to  claim 1 , wherein step a) comprises:
 aI) applying to said sample of step a) a quantifiable affinity ligand capable of selective interaction with the PODXL protein to be evaluated, said application being performed under conditions that enable binding of the affinity ligand to PODXL protein present in the sample; and   aII) quantifying the affinity ligand bound to said sample to evaluate said amount.   
     
     
         14 . Kit for establishing a prognosis of colorectal cancer, which comprises
 a) a quantifiable affinity ligand capable of selective interaction with a PODXL protein;   b) reagents necessary for quantifying the amount of the quantifiable affinity ligand of a);   c) a quantifiable affinity ligand capable of selective interaction with a COX-2 protein; and   d) reagents necessary for quantifying the amount of the quantifiable affinity ligand of c),   wherein the reagents of b) and d) are the same or different.   
     
     
         15 . Method of establishing a prognosis for colorectal cancer, comprising use of a PODXL protein as a prognostic marker. 
     
     
         16 . Method of selection or purification of a prognostic agent for establishing a prognosis for a mammalian subject having a colorectal cancer, comprising use of an antigenically active fragment of a PODXL protein, wherein the antigenically active fragment consists of SEQ ID NO:14. 
     
     
         17 . Method of production of a prognostic agent for establishing a prognosis for a mammalian subject having a colorectal cancer, comprising use of an antigenically active fragment of a PODXL protein as an antigen in an immunization, wherein the antigenically active fragment consists of SEQ ID NO:14. 
     
     
         18 . Affinity ligand capable of selective interaction with a PODXL protein fragment consisting of SEQ ID NO:14. 
     
     
         19 . Method of establishing a prognosis for colorectal cancer, comprising use of an affinity ligand capable of selective interaction with a PODXL protein as a prognostic agent. 
     
     
         20 . Method according to  claim 19 , wherein the affinity ligand is, the affinity ligand according to  claim 18 .