Serological markers for detecting colorectal cancer and their application for inhibiting colorectal cancer cells

Abstract

Embodiments relate to serological markers for detecting the colorectal cancer and applications of the serological markers. A phospholipid scramblase1 (PLSCR1), a stomatin-like protein 2 (STOML2) or a transport protein Sec61β (SEC61β) increases expression in the blood at the earlier stage of the colorectal cancer. Detecting the expression of the PLSCR1, STOML2 or SEC61β protein or an induced autoantibody of each protein in a blood sample is used to diagnose the colorectal cancer. Moreover, the serological marker improves the detection efficiency and the sensitivity in detecting the colorectal cancer and is used to predict the prognosis. The serological markers are applied in preparing a detection device or inhibiting the growth of the colorectal cancer cells.

What is claimed is: 
     
         1 . A serological marker for detecting a colorectal cancer, at least comprising a phospholipid scramblase 1 (PLSCR1), the phospholipid scramblase 1 protein being significant increased in blood samples of colorectal cancer patients and having an amino acid sequence has similarity more than 90% with following sequence 
       
         
           
                 
                 
               
                           10         20         30         40         50         60 
                     
                 
                   MDKQNSQMNA SHPETNLPVG YPPQYPPTAF QGPPGYSGYP GPQVSYPPPP AGHSGPGPAG 
                 
                     
                 
                           70         80         90        100        110        120 
                 
                   FPVPNQPVYN QPVYNQPVGA AGVPWMPAPQ PPLNCPPGLE YLSQIDQILI HQQIELLEVL 
                 
                     
                 
                          130        140        150        160        170        180 
                 
                   TGFETNNKYE IKNSFGQRVY FAAEDTDCCT RNCCGPSRPF TLRIIDNMGQ EVITLERPLR 
                 
                     
                 
                          190        200        210        220        230        240 
                 
                   CSSCCCPCCL QEIEIQAPPG VPIGYVIQTW HPCLPKFTIQ NEKREDVLKI SGPCVVCSCC 
                 
                     
                 
                          250        260        270        280        290        300 
                 
                   GDVDFEIKSL DEQCVVGKIS KHWTGILREA FTDADNFGIQ FPLDLDVKMK AVMIGACFLI 
                 
                     
                 
                          310 
                 
                   DFMFFESTGS QEQKSGVW 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . The serological marker as claimed in  claim 1 , wherein the serological marker further comprises a SEC61β protein or a STOML2 protein. 
     
     
         3 . The serological marker as claimed in  claim 1 , wherein the serological marker further comprises at least one antigen of a protein that is selected from a group consists of: RPH3AL, RPL36, STOML2, P53, Survivin, ANXA4 and SEC61β. 
     
     
         4 . The serological marker as claimed in  claim 1 , wherein the serological marker further comprises an autoantibody of a protein that is selected from a group consists of: PLSCR1, STOML2, and SEC61β. 
     
     
         5 . The serological marker as claimed in  claim 1 , wherein the PLSCR1 protein increases expression in the blood sample at an earlier stage of the colorectal cancer. 
     
     
         6 . The serological marker as claimed in  claim 2 , wherein the STOML2, or the SEC61β protein increases expression in the blood sample at an earlier stage of the colorectal cancer. 
     
     
         7 . The serological marker as claimed in  claim 4 , wherein the autoantibody of PLSCR1, STOML2 or SEC61β increases expression in the blood sample at an earlier stage of the colorectal cancer. 
     
     
         8 . A method for detecting a colorectal cancer, comprising steps of
 establishing a database comprises multiple normal blood samples collected from multiple healthy controls that is confirmed by a clinically medical diagnosis, each blood sample at least has a value of expression of phospholipid scramblase 1 (PLSCR1), the expression values are used to calculate a cutoff value;   collecting a blood sample from a volunteer;   detecting a PLSCR1 protein expression of the tested blood sample; and   comparing the PLSCR1 protein expression of the tested blood sample with the cutoff value, a positive result is defined as the PLSCR1 protein expression of the tested blood sample is higher than the cutoff value and has highly risk be the colorectal cancer.   
     
     
         9 . The method as claimed in  claim 8 , wherein the database further comprises the expression level or the autoantibody response of a protein selected from the group consist of: a STOML2 and a SEC61β, and the tested blood sample is detected the expression of the STOML2 protein or the SEC61β protein, and the autoantibody response of the STOML2 protein or the SEC61β protein. 
     
     
         10 . The method as claimed in  claim 8 , wherein the step of detecting a PLSCR1 expression of the tested blood sample uses an immunoassay. 
     
     
         11 . The method as claimed in  claim 9 , wherein the expression level or the autoantibody response of the STOML2 protein or the SEC61β protein is detected by an immunoassay. 
     
     
         12 . A detection device for detecting a colorectal cancer, comprising
 a sample container is used to contain a blood sample;   a reagent at least comprises an antibody of a phospholipid scramblase 1 (PLSCR1) protein; and   a substrate is provided for developing a signal.   
     
     
         13 . The detection device as claimed in  claim 12 , wherein the reagent further comprises an antibody or a recombinant protein of a protein selected from a group consist of: a STOML2 protein or a SEC61β protein. 
     
     
         14 . The detection device as claimed in  claim 12 , wherein the detection device further comprises a database stores multiple normal blood samples collected from multiple healthy controls that is confirmed by a clinically medical diagnosis, each blood sample at least has an expression value of a phospholipid scramblase 1 (PLSCR1) protein, the multiple expression values are used to calculate a cutoff value. 
     
     
         15 . The detection device as claimed in  claim 13 , wherein the detection device further comprises a database stores multiple normal blood samples collected from multiple healthy controls that is confirmed by a clinically medical diagnosis, each blood sample at least has an expression value of a STOML2 protein or a SEC61β protein, the expression values are used to calculate a cutoff value. 
     
     
         16 . The detection device as claimed in  claim 12 , wherein the reagent further comprises a protein selected from a group consist of a STOML2 protein and a SEC61β protein. 
     
     
         17 . The detection device as claimed in  claim 12 , wherein the reagent further comprises a antibody of a protein selected from a group consist of PLSCR1, STOML2 and SEC61β. 
     
     
         18 . The detection device as claimed in  claim 12 , wherein the reagent further comprises an antigen selected from a group consist of RPH3AL, RPL36, STOML2, P53, Survivin, ANXA4 and SEC61β. 
     
     
         19 . A detection device for detecting a colorectal cancer, comprising
 a sample container is used to contain a blood sample;   a reagent at least comprises a recombinant protein of phospholipid scramblase 1 (PLSCR1) protein; and   a substrate is provided for developing a signal.   
     
     
         20 . The detection device as claimed in  claim 19 , wherein the reagent further comprises an antibody or a recombinant protein of a protein selected from a group consists of: STOML2 and SEC61β. 
     
     
         21 . The detection device as claimed in  claim 19 , wherein the detection device further comprises a database stores multiple normal blood samples collected from multiple healthy controls that is confirmed by a clinically medical diagnosis, each blood sample at least has a value of autoantibody response of phospholipid scramblase 1 (PLSCR1) protein, the values of autoantibody response are used to calculate a cutoff value. 
     
     
         22 . The detection device as claimed in  claim 20 , wherein the detection device further comprises a database stores multiple normal blood samples collected from multiple healthy controls that is confirmed by a clinically medical diagnosis, each blood sample at least has a value of autoantibody response of a STOML2 protein or a SEC61β protein, the values of autoantibody response are used to calculate a cutoff value. 
     
     
         23 . The detection device as claimed in  claim 22 , wherein the reagent further comprises a protein selected from a group consists of a STOML2 protein and a SEC61β protein. 
     
     
         24 . The detection device as claimed in  claim 22 , wherein the reagent further comprises an antibody of a protein selected from a group consist of PLSCR1 protein, STOML2 protein and SEC61β protein. 
     
     
         25 . The detection device as claimed in  claim 22 , wherein the reagent further comprises an antigen selected from a group consist of RPH3AL, RPL36, STOML2, P53, Survivin, ANXA4 and SEC61β. 
     
     
         26 . A method for inhibiting the growth of colorectal cancer cells, comprising steps of
 preparing an anti-phospholipid scramblase 1 (PLSCR1) antibody; and   reacting the anti-PLSCR1 antibody with the colorectal cancer cells.   
     
     
         27 . The method as claimed in  claim 26 , wherein the anti-PLSCR1 antibody is formed as an injection, a tablet or a powder, used in the therapy of colorectal cancer. 
     
     
         28 . A serological marker for detecting a colorectal cancer, at least comprising a SEC61β protein being significant increased in the blood samples of the colorectal cancer patients and having an amino acid sequence has similarity more than 90% with following sequence 
       
         
           
                 
                 
               
                           10         20         30         40         50         60 
                     
                 
                   MPGPTPSGTN VGSSGRSPSK AVAARAAGST VRQRKNASCG TRSAGRTTSA GTGGMWRFYT 
                 
                     
                 
                           70         80         90 
                 
                   EDSPGLKVGP VPVLVMSLLF IASVFMLHIW GKYTRS 
                 
             
                
                
                
                
                
               
            
           
         
       
     
     
         29 . The serological marker as claimed in  claim 28 , wherein the serological marker further comprises a phosphoholipid scramblase 1 (PLSCR1) protein or a STOML2 protein. 
     
     
         30 . The serological marker as claimed in  claim 28 , wherein the serological marker further comprises at least one antigen of a protein that is selected from a group consists of: RPH3AL, RPL36, STOML2, P53, Survivin and ANXA4. 
     
     
         31 . The serological marker as claimed in  claim 28 , wherein the serological marker further comprises an autoantibody of a protein that is selected from a group consists of: PLSCR1, STOML2, and SEC61β. 
     
     
         32 . The serological marker as claimed in  claim 28 , wherein the SEC61β protein increases expression in the blood sample at an earlier stage of the colorectal cancer. 
     
     
         33 . The serological marker as claimed in  claim 29 , wherein the PLSCR1 protein or the STOML2 protein increases expression in the blood sample at an earlier stage of the colorectal cancer. 
     
     
         34 . The serological marker as claimed in  claim 31 , wherein the autoantibody of the PLSCR1 protein, STOML2 protein or the SEC61β protein increases expression in the blood sample at an earlier stage of the colorectal cancer. 
     
     
         35 . A serological marker for detecting a colorectal cancer, at least comprising an STOML2 protein being significant increased in the blood samples of the colorectal cancer patients and having an amino acid sequence has similarity more than 90% with following sequence 
       
         
           
                 
                 
               
                            10         20         30         40         50         60 
                     
                 
                   MLARAARGTG ALLLRGSLLA SGRAPRRASS GLPRNTVVLF VPQQEAWVVE RMGRFHRILE 
                 
                     
                 
                            70         80         90        100       110        120 
                 
                   PGLNILIPVL DRIRYVQSLK EIVINVPEQS AVTLDNVTLQ IDGVLYLRIM DPYKASYGVE 
                 
                     
                 
                          130        140        150        160        170         180 
                 
                   DPEYAVTQLA QTTMRSELGK L5LDKVFRER ESLNASIV DAINQAADCWGI RCLRYEIKDI 
                 
                     
                 
                           190        200        210        220        230        240 
                 
                   HVPPRVKESM QMQVEAERRK RATVLESEGT RESAINVAEG KKQAQILASE AEKAEQINQA 
                 
                     
                 
                           250        260        270        280        290        300 
                 
                   AGEASAVLAK AKAKAEAIRI LAAALTQHNG DAAASLTVAE QYVSAFSKLA KDSNTILLPS 
                 
                     
                 
                           310        320        330        340        350 
                 
                   NPGDVTSMVA QAMGVYGALT KAPVPGTPDS LSSGSSRDVQ GTDASLDEEL DRVKMS 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         36 . The serological marker as claimed in  claim 35 , wherein the serological marker further comprises phosphoholipid scramblase 1 (PLSCR1) or a SEC61β protein. 
     
     
         37 . The serological marker as claimed in  claim 35 , wherein the serological marker further comprises at least one antigen of a protein that is selected from a group consists of: RPH3AL, RPL36, P53, Survivin, ANXA4 and SEC61β. 
     
     
         38 . The serological marker as claimed in  claim 35 , wherein the serological marker further comprises an autoantibody of a protein that is selected from a group consists of: PLSCR1, STOML2, and SEC61β. 
     
     
         39 . The serological marker as claimed in  claim 35 , wherein the STOML2 protein increases expression in the blood sample at an earlier stage of the colorectal cancer. 
     
     
         40 . The serological marker as claimed in  claim 36 , wherein the PLSCR1, or the SEC61β protein increases expression in the blood sample at an earlier stage of the colorectal cancer. 
     
     
         41 . The serological marker as claimed in  claim 38 , wherein the autoantibody of the PLSCR1 protein, the STOML2 protein or the SEC61β protein increases response level in the blood sample at an earlier stage of the colorectal cancer.