Compositions and methods for diagnosing lung cancers using gene expression profiles

Abstract

Methods and compositions are provided for diagnosing lung cancer in a mammalian subject by use of 10 or more selected genes, e.g., a gene expression profile, from the blood of the subject which is characteristic of disease. The gene expression profile includes 10 or more genes of Table I or Table II herein.

1 . A composition for diagnosing the existence or evaluating the progression of a lung cancer in a mammalian subject, said composition comprising at least 10 polynucleotides or oligonucleotides, wherein each polynucleotide or oligonucleotide hybridizes to a different gene, gene fragment, gene transcript or expression product in a sample selected from the genes of Table I. 
     
     
         2 . The composition of  claim 1 , wherein at least one polynucleotide or oligonucleotide is attached to a detectable label. 
     
     
         3 . The composition of  claim 2 , wherein each polynucleotide or oligonucleotide is attached to a different detectable label. 
     
     
         4 . The composition of  claim 1 , further comprising a capture oligonucleotide, which hybridizes to at least one polynucleotide or oligonucleotide. 
     
     
         5 . The composition of  claim 4 , wherein the capture oligonucleotide is capable of hybridizing to each polynucleotide or oligonucleotide. 
     
     
         6 . The composition of  claim 4 , wherein the capture oligonucleotide binds to a substrate. 
     
     
         7 . The composition of  claim 6 , further comprising a substrate to which the capture oligonucleotide binds. 
     
     
         8 . The composition of  claim 1 , comprising at least 15 polynucleotides or oligonucleotides. 
     
     
         9 . The composition of  claim 1 , comprising at least 25 polynucleotides or oligonucleotides. 
     
     
         10 . The composition of  claim 1 , comprising at least 50 polynucleotides or oligonucleotides. 
     
     
         11 . The composition of  claim 1 , comprising at least 100 polynucleotides or oligonucleotides. 
     
     
         12 . The composition of  claim 1 , comprising at least 500 polynucleotides or oligonucleotides. 
     
     
         13 . The composition of  claim 1 , comprising polynucleotides or oligonucleotides capable of hybridizing to each different gene, gene fragment, gene transcript or expression product listed in Table I. 
     
     
         14 . A kit comprising the composition of  claim 1  and an apparatus for sample collection. 
     
     
         15 . A method for diagnosing the existence or evaluating a lung cancer in a mammalian subject comprising identifying changes in the expression of 10 or more genes in the sample of said subject, said genes selected from the genes of Table I; and comparing said subject's gene expression levels with the levels of the same genes in a reference or control, wherein changes in expression of the subject's genes from those of the reference correlates with a diagnosis or evaluation of a lung cancer. 
     
     
         16 . The method according to  claim 15 , wherein said diagnosis or evaluation comprise one or more of a diagnosis of a lung cancer, a diagnosis of a benign nodule, a diagnosis of a stage of lung cancer, a diagnosis of a type or classification of a lung cancer, a diagnosis or detection of a recurrence of a lung cancer, a diagnosis or detection of a regression of a lung cancer, a prognosis of a lung cancer, or an evaluation of the response of a lung cancer to a surgical or non-surgical therapy. 
     
     
         17 . The method according to  claim 15 , wherein said changes comprise an upregulation of one or more selected genes in comparison to said reference or control or a downregulation of one or more selected genes in comparison to said reference or control. 
     
     
         18 . The method according to  claim 15 , further comprising identifying the size of a lung nodule in the subject. 
     
     
         19 . The method according to  claim 15 , wherein the specificity is about 46% at about 90% sensitivity or about 54% at about 90% for nodules <10 mm. 
     
     
         20 . The method according to  claim 15 , wherein the accuracy is about 88% for nodules ≤8 mm, about 75% for nodules ≥8 mm and <12 mm, about 68% for nodules >12 mm and ≤16 mm, and about 53% for nodules >16 mm.