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.

1 . A composition for diagnosing the existence or evaluating the progression of a lung cancer in a mammalian subject, said composition comprising:
 (a) three or more polynucleotides or oligonucleotides, wherein each polynucleotide or oligonucleotide hybridizes to a different gene, gene fragment, gene transcript or expression product from mammalian peripheral blood mononuclear cells (PBMC), or   (b) three or more ligands, wherein each ligand binds to a different gene expression product from mammalian peripheral blood mononuclear cells (PBMC),   wherein said gene, gene fragment, gene transcript or expression product is selected from the group consisting of: (i) the genes of Table I; (ii) the genes of Table II; (iii) the genes of Table III; (iv) the genes of Table IV, (v) the genes of Table V; (vi) the genes of Table VI; and (vii) the genes of Table VII.   
     
     
         2 . The composition according to  claim 1 , which is a reagent comprising a substrate upon which said polynucleotides or oligonucleotides or ligands are immobilized. 
     
     
         3 . The composition according to  claim 1 , wherein said ligands or said expression products are proteins or peptides. 
     
     
         4 . The composition according to  claim 1 , comprising a microarray, a microfluidics card, a chip or a chamber. 
     
     
         5 . The composition according to  claim 1 , which is a kit containing said three or more polynucleotides or oligonucleotides or ligands. 
     
     
         6 . The composition according to  claim 5 , 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. 
     
     
         7 . The composition according to  claim 1 , wherein one or more polynucleotide or oligonucleotide or ligand is associated with a detectable label. 
     
     
         8 . The composition according to  claim 1 , wherein the lung cancer is a non-small cell lung cancer. 
     
     
         9 . The composition according to  claim 1 , wherein said selected genes comprise 4 to 50 genes of any of (i) to (vii). 
     
     
         10 . The composition according to  claim 1 , wherein:
 (a) said genes from Table I comprise three or more genes selected from the group consisting of IGSF6, HSPA8(A), LYN, DNCL1, HSPA1A, DPYSL2, HAGK, HSPA8(I), NFKBIA, FGL2, CALM2, CCL5, RPS2, DDIT4 and Clorf63;   (b) said genes from Table II comprise three or more genes selected from the group consisting of ETS1, CCL5, DDIT4, CXCR4, DNCL1, MS4ABA, ATP5B, HSPA8(A), ADM PTPN6, ARHGAP9, S100A8, DPYSL2, HSPA1A, and NFKBIA;   (c) said genes from Table III comprise three or more genes selected from the group consisting of TSC22D3, CXCR4, DNCL1, RPS3, DDIT4, GAMB, BTG1, HSPA8(I), RPL12, SLA, RUNX3, MGC17330, HSPA1A, IL18RAP and CIRBP;   (d) said genes in rank order 1 to 29 of Table V;   (e) said genes comprising the 24 genes of Table VII;   (f) said selected genes comprising 4 or more genes of Table VI.   
     
     
         11 . 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 peripheral blood mononuclear cells (PBMC) of said subject, said genes selected from the group consisting of: (a) the genes of Table I; (b) the genes of Table II; (c) the genes of Table III; and (d) the genes of Table IV, (e) the genes of Table V; (f) the genes of Table VI; and (g) the genes of Table VII, with the levels of the same genes in the PBMC of a reference or control, 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. 
     
     
         12 . The method according to  claim 11 , further comprising using the composition of  claim 1  for said diagnosis. 
     
     
         13 . The method according to  claim 11 , further comprising using the composition of  claim 9  for said diagnosis. 
     
     
         14 . The method according to  claim 11 , further comprising using the composition of  claim 10  for said diagnosis.