Armet as a marker for cancer

Abstract

Disclosed is a method aiding in the assessment of cancer. More specifically disclosed is the use of the arginine-rich metastasized in early tumors protein (=ARMET) as a universal marker of different cancer types. ARMET aids in the assessment of pulmonary or lung cancer (LC) or of colon cancer, e.g., of non-small cell lung carcinoma (NSCLC) or colorectal cancer (CRC), but also likely of other specific types of cancer. Such specific cancer types are, e.g., breast, ovary, cervix, head and neck, endometrium, melanoma, bladder, kidney, pancreas, prostate, esophagus, stomach or bile duct cancer. Further disclosed is a method for assessing cancer from a liquid sample, derived from an individual by measuring ARMET in the sample. Measurement of ARMET can, e.g., be used in the early detection of cancer or in the surveillance of patients who undergo surgery.

What is claimed is: 
     
         1 . A method for assessing lung cancer in a patient, the method comprising:
 contacting, in vitro, a portion of a blood, serum or plasma sample obtained from the patient with an antibody having specific binding affinity for arginine-rich, mutated in early stage tumors (ARMET) protein, thereby forming a complex of the antibody and ARMET protein, the antibody having a detectable label;   quantifying a signal from the detectable label of the antibody comprising the complex formed in said step of contacting, the signal being proportional to an ARMET concentration in the sample, whereby ARMET concentration in the sample is calculated;   comparing the ARMET concentration in the sample to an ARMET control concentration; and   diagnosing lung cancer in the patient if the ARMET concentration in the sample is greater than the ARMET control concentration.   
     
     
         2 . The method according to  claim 1 , wherein the detectable label is one of digoxygenin and peroxidase. 
     
     
         3 . The method according to  claim 1 , wherein the antibody is a recombinant polyclonal antibody. 
     
     
         4 . The method according to  claim 1 , wherein the patient is identified as being at higher than average risk of lung cancer. 
     
     
         5 . The method according to  claim 4 , wherein the patient is at least one of a smoker, an ex-smoker, an uranium-exposed worker, a quartz-exposed worker and an asbestos-exposed worker. 
     
     
         6 . The method according to  claim 1  further comprising the steps of:
 coupling the complex comprising the antibody and ARMET protein to a solid surface; 
 separating the complex coupled to the solid surface from antibody not comprising the complex; and 
 exposing the detection label of the antibody comprising the complex coupled to the solid support to a substrate, whereby a signal is produced, said steps of coupling, separating and exposing occurring after said step of contacting and prior to said step of quantifying. 
 
     
     
         7 . The method according to  claim 6 , wherein the solid surface is one of a microwell and a bead. 
     
     
         8 . The method according to  claim 6 , wherein said step of coupling comprises incubating a capture antibody having one of biotin and streptavidin coupled thereto with the sample, wherein the solid surface having the other of biotin and streptavidin coupled thereto. 
     
     
         9 . The method according to  claim 6 , wherein the substrate comprises ABTS solution. 
     
     
         10 . The method of  claim 1  further comprising the steps of:
 contacting, in vitro, a portion of the sample obtained from the patient with an antibody having specific binding affinity for an additional marker of cancer, thereby forming a complex of the antibody having specific binding affinity for the additional marker and the additional marker of cancer, the antibody having specific binding affinity for the additional marker having a detectable label; 
 quantifying a signal resultant from the detectable label of the antibody having specific binding affinity for the additional marker comprising the complex formed in said step of contacting, the signal being proportional to the additional marker of cancer concentration in the sample; and 
 comparing the additional marker of cancer concentration in the sample to a control concentration for the additional marker of cancer, 
 
       wherein said step of diagnosing further comprises diagnosing lung cancer in the patient if both ARMET concentration in the sample is greater than the ARMET control concentration and the additional marker of cancer concentration is greater than the control concentration for the additional marker of cancer. 
     
     
         11 . The method according to  claim 10 , wherein the additional marker of cancer is selected from the group consisting of soluble 30 kDa fragment of cytokeratin 19 (Cyfra 21-1), carcinoembryogenic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), squamous cell carcinoma antigen (SCC), carbohydrate antigen 125 (CA 125), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (proGRP), prostate specific antigen (PSA), and nicotinamide N-methyltransferase (NNMT). 
     
     
         12 . The method according to  claim 1 , wherein the ARMET control concentration has a specificity of at least 90%, the specificity calculated from a receiver-operating characteristics analysis of a subgroup of samples comprising a plurality of patients known not to have heart failure at the time the samples were obtained. 
     
     
         13 . A method of managing treatment of a patient having lung cancer, the method comprising:
 contacting, in vitro, a portion of a blood, serum or plasma sample obtained from the patient prior to a treatment regimen with an antibody having specific binding affinity for arginine-rich, mutated in early stage tumors (ARMET) protein, thereby forming a complex of the antibody and ARMET protein, the antibody having a detectable label;   quantifying a signal from the detectable label of the antibody comprising the complex formed in said step of contacting, the signal being proportional to an ARMET concentration in the sample obtained prior to the treatment regimen, whereby ARMET concentration in the sample is calculated;   comparing the ARMET concentration in the sample to an ARMET control concentration; and   treating the patient with the treatment regimen for lung cancer if the ARMET concentration in the sample is greater than the ARMET control concentration.   
     
     
         14 . The method according to  claim 13 , wherein treatment comprises surgical resection, chemotherapy, or both. 
     
     
         15 . The method of  claim 13  further comprising the steps of:
 contacting, in vitro, a portion of a sample obtained from the patient following said step of treating, with the antibody, whereby the complex forms; 
 quantifying a signal from the detectable label of the antibody comprising the complex formed in said step of contacting, the signal being proportional to ARMET concentration in the sample obtained following said step of treating, whereby ARMET concentration in the sample obtained following said step of treating is calculated; and 
 discontinuing the treatment regimen of the patient if the ARMET concentration in the sample obtained following said step of treating is less than the ARMET concentration in the sample obtained prior to the treatment regimen. 
 
     
     
         16 . The method of  claim 13  further comprising the steps of:
 contacting, in vitro, a portion of the sample obtained from the patient prior to the treatment regimen with an antibody having specific binding affinity for an additional marker of cancer, thereby forming a complex of the antibody having specific binding affinity for the additional marker and the additional marker of cancer, the antibody having specific binding affinity for the additional marker having a detectable label; 
 quantifying a signal from the detectable label of the antibody having specific binding affinity for the additional marker comprising the complex formed in said step of contacting, the signal being proportional to the additional marker of cancer concentration in the sample obtained prior to treatment; and 
 comparing the additional marker of cancer concentration in the sample to a control concentration for the additional marker of cancer, 
 
       wherein said step of treating the patient further comprises treating the patient for lung cancer if both ARMET concentration in the sample is greater than the ARMET control concentration and the additional marker of cancer concentration is greater than the control concentration for the additional marker of cancer. 
     
     
         17 . The method according to  claim 16 , wherein the additional marker of cancer is selected from the group consisting of soluble 30 kDa fragment of cytokeratin 19 (Cyfra 21-1), carcinoembryogenic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), squamous cell carcinoma antigen (SCC), carbohydrate antigen 125 (CA 125), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (proGRP), prostate specific antigen (PSA), and nicotinamide N-methyltransferase (NNMT). 
     
     
         18 . The method according to  claim 13 , wherein the detectable label is one of digoxygenin and peroxidase. 
     
     
         19 . The method according to  claim 13  further comprising the steps of:
 coupling the complex comprising the antibody and ARMET protein to a solid surface; 
 separating the complex coupled to the solid surface from antibody not comprising the complex; and 
 exposing the detection label of the antibody comprising the complex coupled to the solid support to a substrate, whereby a signal is produced, said steps of coupling, separating and exposing occurring after said step of contacting and prior to said step of quantifying. 
 
     
     
         20 . The method according to  claim 19 , wherein the solid surface is one of a microwell and a bead.