Method for diagnosing lung cancers using gene expression profiles in peripheral blood mononuclear cells

Abstract

Methods and compositions are provided for diagnosing lung cancer in a mammalian subject by use of three or more selected gene, e.g., a gene expression profile, from the peripheral blood mononuclear cells (PBMC) of the subject which is characteristic of disease, a stage of the disease, or enables prognosis of recurrence of disease. The gene expression profile includes three or more genes of Table I, Table II, Table III, Table IV, Table V, Table VI or Table VII herein. Detection of changes in expression in the selected genes forming the gene expression profile from that of a reference gene expression profile are correlated with non-small cell lung cancer (NSCLC). One composition for use in such diagnosis includes three or more PCR primer-probe sets, wherein each primer-probe set amplifies a different polynucleotide sequence from the gene expression profile. Another composition for similar use contains a plurality of polynucleotides immobilized on a substrate, which probes hybridize to three or more gene expression products from genes in the gene expression profile. Still another composition involves detection of the protein expression products of genes from the gene expression profile.

What is claimed is: 
     
         1 . (canceled) 
     
     
         2 . A composition for diagnosing the existence or evaluating the progression of a lung cancer in a mammalian subject, said composition comprising three or more polynucleotides, oligonucleotides or ligands, wherein each polynucleotide, oligonucleotide or ligand hybridizes to a different gene, gene fragment or gene transcript selected from:
 i. AKR1C3;   ii. ATP5B;   iii. C15orf39;   iv. CLIC3;   v. CST7;   vi. CTDSP2;   vii. DDIT4;   viii. DGUOK;   ix. EIF2B4;   x. FRAT2;   xi. GZMB;   xii. HAVCR2;   xiii. HLA-DMB;   xiv. KCTD12;   xv. LYN;   xvi. MID1IP1;   xvii. MS4A6A;   xviii. MYADM;   xix. NAGK;   xx. RAB10;   xxi. RBM14;   xxii. RXRA;   xxiii. S100A8;   xxiv. SAMSN1; and   xxv. SH2D3C.   
     
     
         3 . The composition according to  claim 2 , wherein each polynucleotide, oligonucleotide or ligand hybridizes to a mRNA transcript. 
     
     
         4 . The composition according to  claim 2 , which is a reagent comprising a substrate upon which said polynucleotides, oligonucleotides or ligands are immobilized. 
     
     
         5 . The composition according to  claim 2 , comprising a microarray, a microfluidics card, a chip or a chamber. 
     
     
         6 . The composition according to  claim 2 , which is a kit containing said three or more polynucleotides or oligonucleotides or ligands. 
     
     
         7 . The composition according to  claim 6 , wherein said polynucleotides or oligonucleotides are each part of a primer-probe set, and said kit comprises both primer and probe, wherein each said primer-probe set amplifies a different gene, gene fragment or gene expression product. 
     
     
         8 . The composition according to  claim 2 , wherein said polynucleotides, oligonucleotides or ligands are attached to silica beads. 
     
     
         9 . The composition according to  claim 2 , wherein one or more polynucleotide or oligonucleotide or ligand is associated with a detectable label. 
     
     
         10 . The composition according to  claim 2 , wherein the lung cancer is a non-small cell lung cancer. 
     
     
         11 . The composition according to  claim 2 , wherein said selected genes comprise 4 to 25 genes of any of (i) to (xxv). 
     
     
         12 . The composition according to  claim 2 , wherein the selected genes comprise at least 10 genes of any of (i) to (xxv). 
     
     
         13 . The composition according to  claim 2 , wherein the selected genes comprise at least 15 genes of any of (i) to (xxv). 
     
     
         14 . The composition according to  claim 2 , wherein the selected genes comprise at least 20 genes of any of (i) to (xxv). 
     
     
         15 . The composition according to  claim 2 , wherein the selected genes comprise at least 24 genes of any of (i) to (xxv). 
     
     
         16 . The composition according to  claim 2 , wherein the selected genes comprise all 25 genes of any of (i) to (xxv). 
     
     
         17 . The composition according to  claim 2 , wherein the selected genes comprise DDIT4 and GZMB. 
     
     
         18 . A method for diagnosing the existence or evaluating a lung cancer in a mammalian subject comprising identifying changes in the expression of three or more genes from the whole blood of said subject as compared to the levels of the same genes a reference or control, said genes selected from:
 i. AKR1C3;   ii. ATP5B;   iii. C15orf39;   iv. CLIC3;   v. CST7;   vi. CTDSP2;   vii. DDIT4;   viii. DGUOK;   ix. EIF2B4;   x. FRAT2;   xi. GZMB;   xii. HAVCR2;   xiii. HLA-DMB;   xiv. KCTD12;   xv. LYN;   xvi. MID1IP1;   xvii. MS4A6A;   xviii. MYADM;   xix. NAGK;   xx. RAB10;   xxi. RBM14;   xxii. RXRA;   xxiii. S100A8;   xxiv. SAMSN1; and   xxv. SH2D3C;   and diagnosing one or more of a diagnosis of a lung cancer, 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.   
     
     
         19 . The method according to  claim 18 , wherein the levels of gene expression are measured by mRNA levels. 
     
     
         20 . The method according to  claim 18 , further comprising stabilizing the mRNA in the whole blood sample of the subject prior and measuring mRNA levels of the three or more genes prior to identifying changes in the expression.