Compositions and methods for prognosis and therapy of liver cancer

Abstract

This invention provides a composition comprising the following polynucleotide probes: IL7R (AA485865), NDRG1 (AA486403), EST1 (H50345), TRPC1 (AA017132), GFRA1 (AA512935), EST2 (AA454543), CLDN10 (R54559), DNALI1 (R93087), RBP5 (AA453198), EST3 (AA621761), EST4 (N63706), PCOLCE (AA670200), TDO2 (T72398), EST5 (T47454), HIST1H2BD (N33927), PXMP2 (N70714), ACAS2 (AA455146), ANAPC7 (T68445), EST6 (AA576580), RBP5 (N92148), ANXA1 (H63077), CKB (AA894557), ITGBL1 (N52533), KPNA2 (AA676460), EST7 (W90740) and MEG3 (W85841). This invention further provides methods for determining the likelihood of recurrence of hepatocellular carcinoma (HCC) in a subject afflicted with HCC, for determining the likelihood of death of a subject afflicted with HCC or for determining whether to administer adjuvant therapy.

1 . A composition comprising the following polynucleotide probes: IL7R (AA485865), NDRG1 (AA486403), EST1 (H50345), TRPC1 (AA017132), GFRA1 (AA512935), EST2 (AA454543), CLDN10 (R54559), DNALI1 (R93087), RBP5 (AA453198), EST3 (AA621761), EST4 (N63706), PCOLCE (AA670200), TDO2 (T72398), EST5 (T47454), HIST1H2BD (N33927), PXMP2 (N70714), ACAS2 (AA455146), ANAPC7 (T68445), EST6 (AA576580), RBP5 (N92148), ANXA1 (H63077), CKB (AA894557), ITGBL1 (N52533), KPNA2 (AA676460), EST7 (W90740) and MEG3 (W85841), or any combination thereof.  
     
     
         2 . The composition in accordance with  claim 1 , wherein the polynucleotide probes are complementary DNAs.  
     
     
         3 . The composition in accordance with  claim 1 , wherein the polynucleotide probes are clone cDNAs.  
     
     
         4 . The composition in accordance with  claim 1 , wherein the polynucleotide probes are immobilized on a substrate.  
     
     
         5 . The composition in accordance with  claim 4 , wherein the polynucleotide probes are hybridizable array elements.  
     
     
         6 . A composition comprising the following polynucleotide probes: IL7R (AA485865), NDRG1 (AA486403), EST1 (H50345), TRPC1 (AA017132), GFRA1 (AA512935), EST2 (AA454543), CLDN10 (R54559), DNALI1 (R93087), RBP5 (AA453198), EST3 (AA621761), EST4 (N63706) and PCOLCE (AA670200).  
     
     
         7 . The composition in accordance to  claim 6  further comprising one or more of the following polynucleotide probes: TDO2 (T72398), EST5 (T47454), HIST1H2BD (N33927), PXMP2 (N70714), ACAS2 (AA455146), ANAPC7 (T68445), EST6 (AA576580), RBP5 (N92148), ANXA1 (H63077), CKB (AA894557), ITGBL1 (N52533), KPNA2 (AA676460), EST7 (W90740) and MEG3 (W85841).  
     
     
         8 . The composition in accordance with  claim 6 , wherein the polynucleotide probes are complementary DNAs.  
     
     
         9 . The composition in accordance with  claim 6 , wherein the polynucleotide probes are clone cDNAs.  
     
     
         10 . The composition in accordance with  claim 6 , wherein the polynucleotide probes are immobilized on a substrate.  
     
     
         11 . The composition in accordance with  claim 4 , wherein the polynucleotide probes are hybridizable array elements.  
     
     
         12 . A method for determining the likelihood of recurrence of hepatocellular carcinoma (HCC) in a subject afflicted with HCC, comprising: 
 (a) obtaining a tumor sample from the subject;    (b) determining the gene expression pattern of the composition of  claim 6  in the tumor sample;    (c) calculating the prognostic gene score of the gene expression pattern; and    (d) comparing the prognostic gene score to a prognostic gene score associated with recurrence of HCC, thereby determining the likelihood of recurrence of HCC in the subject.    
     
     
         13 . The method of  claim 12 , wherein the gene expression pattern is determined by microarray.  
     
     
         14 . The method of  claim 12 , wherein the gene expression pattern is determined by RT-PCR.  
     
     
         15 . The method of  claim 12 , wherein a prognostic gene score of less than 0.416 indicates a low probability of recurrence of HCC.  
     
     
         16 . The method of  claim 12 , wherein a prognostic gene score of at least 0.416 indicates a high probability of recurrence of HCC.  
     
     
         17 . A method for determining the likelihood of hepatocellular carcinoma (HCC) to cause death of an afflicted subject, comprising: 
 (a) obtaining a tumor sample from the subject;    (b) determining the gene expression pattern of the composition of  claim 6  in the tumor sample;    (c) calculating the prognostic gene score of the gene expression pattern; and    (d) comparing the prognostic gene score to a prognostic gene score associated with death caused by HCC, thereby determining the likelihood of HCC-associated death of the subject.    
     
     
         18 . The method of  claim 17 , wherein a prognostic gene score of less than 0.600 indicates a low probability of HCC-associated death.  
     
     
         19 . The method of  claim 17 , wherein a prognostic gene score of at least 0.600 indicates a high probability of HCC-associated death.  
     
     
         20 . A method of determining whether to administer adjuvant therapy for a subject afflicted with hepatocellular carcinoma (HCC) comprising: 
 (a) obtaining a tumor sample from the subject;    (b) determining the expression pattern of the composition of  claim 6  in the tumor sample; and    (c) calculating the prognostic gene score of the expression pattern; and    (d) comparing the prognostic gene score to a prognostic gene score associated with recurrence of HCC, thereby determining whether to administer adjuvant therapy.    
     
     
         21 . The method of  claim 20 , wherein a prognostic gene score of at least 0.416 indicates adjuvant therapy should be administered.  
     
     
         22 . The method of  claim 20 , wherein a prognostic gene score of less than 0.416 indicates adjuvant therapy should not be administered.  
     
     
         23 . A method for determining the prognosis of a subject afflicted with hepatocellular carcinoma (HCC), comprising: 
 (a) obtaining a tumor sample from the subject;    (b) determining the gene expression pattern of the composition of  claim 6  in the tumor sample;    (c) calculating the prognostic gene score of the gene expression pattern, wherein a prognostic gene score of less than 0.416 indicates a good prognosis, a prognostic gene score of at least 0.416 but less than 0.600 indicates an intermediary prognosis, and a prognostic gene score of at least 0.600 indicates a poor prognosis.    
     
     
         24 . A method for determining the prognosis of a subject afflicted with hepatocellular carcinoma (HCC), comprising: 
 (a) obtaining a tumor sample from the subject;    (b) determining the level of CLDN10 nucleic acid transcript in the tumor sample;    (c) comparing the level of CLDN10 nucleic acid transcript from step (b) with the level of CLDN10 nucleic acid transcript in the normal tissue sample, whereby a higher level of CLDN10 nucleic acid transcript in step (b) indicates a poor prognosis.    
     
     
         25 . A method for determining the prognosis of a subject afflicted with hepatocellular carcinoma (HCC), comprising: 
 (a) obtaining a tumor sample from the subject;    (b) determining the level of AA454543 nucleic acid transcript in the tumor sample;    (c) comparing the level of AA454543 nucleic acid transcript from step (b) with the level of AA454543 nucleic acid transcript in the normal tissue sample, whereby a higher level of AA454543 nucleic acid transcript in step (b) indicates a poor prognosis.    
     
     
         26 . A method for determining the prognosis of a subject afflicted with hepatocellular carcinoma (HCC), comprising: 
 (a) obtaining a tumor sample from the subject;    (b) determining the level of DNALI1 nucleic acid transcript in the tumor sample;    (c) comparing the level of DNALI1 nucleic acid transcript from step (b) with the level of DNALI1 nucleic acid transcript in the normal tissue sample, whereby a higher level of DNALI1 nucleic acid transcript in step (b) indicates a poor prognosis.    
     
     
         27 . A method for determining the likelihood of recurrence of hepatocellular carcinoma (HCC) in a subject afflicted with HCC, comprising: 
 (a) obtaining a serum sample from the subject;    (b) detecting the presence of a DNALI1 nucleic acid transcript; and    (b) determining the polymorphism present at nucleotide 194 of codon 65 of the DNALI1 nucleic acid transcript of step (c) to identify which allele is present, whereby the presence of a T-allele indicates a high probability of recurrence of HCC.