Diagnostic for lung disorders using class prediction

Abstract

The present invention provides methods for diagnosis and prognosis of lung cancer using expression analysis of one or more groups of genes, and a combination of expression analysis with bronchoscopy. The methods of the invention provide far superior detection accuracy for lung cancer when compared to any other currently available method for lung cancer diagnostic or prognosis. The invention also provides methods of diagnosis and prognosis of other lung diseases, particularly in individuals who are exposed to air pollutants, such as cigarette or cigar smoke, smog, asbestos and the like air contaminants or pollutants.

We claim: 
     
         1 . A method of diagnosing lung cancer in an individual comprising the steps of:
 a) measuring a biological sample comprising lung epithelial tissue from the individual for the expression of at least 20 gene transcripts from Table 6;   b) comparing the expression of the at least 20 gene transcripts to a control sample of those transcripts from individuals without cancer,   wherein increased expression of the gene transcripts as indicated by a negative score in the last column of Table 6 and/or decreased expression of the gene transcripts as indicated by a positive score in the last column of Table 6 is indicative of the individual having lung cancer.   
     
     
         2 . The method of  claim 1 , wherein at least 40 gene transcripts are measured. 
     
     
         3 . The method of  claim 1 , wherein at least 60 gene transcripts are measured. 
     
     
         4 . The method of  claim 1 , wherein at least 70 gene transcripts are measured. 
     
     
         5 . The method of  claim 1 , wherein the gene transcript measured is set forth in Table 5. 
     
     
         6 . The method of  claim 1 , wherein the gene transcript measured is set forth in Table 7. 
     
     
         7 . The method of  claim 1 , wherein the gene transcript measured is set forth in Table 1 wherein the measurement of the gene transcript relative to the control uses the third column of Table 1 setting forth direction of expression in lung cancer to determine if the individual has lung cancer. 
     
     
         8 . The method of  claim 7 , wherein the transcript measured is at least Table 3. 
     
     
         9 . The method of  claim 7 , wherein the transcript used is at least the transcripts set forth in Table 4. 
     
     
         10 . A method of diagnosing a lung disease in an individual exposed to air pollutant comprising the steps of
 a) measuring expression profile of a gene group in the sample from a test individual; and   b) comparing the expression profile of the test individual to an expression profile of a first control individual exposed to similar air pollutant who does not have the lung disease and the expression profile of a second control individual exposed to similar air pollutants who has the lung disease,   wherein similarity of the expression profile of the test individual with the expression profile of the first control rather than that of the second control is indicative of the test individual being not affected with the lung disease and wherein similarity of the expression profile of the test individual with the expression profile of the second control individual rather than that of the first control individual is indicative of the test individual being affected or at high risk of developing the lung disease.   
     
     
         11 . The method of  claim 7 , wherein the gene group comprises at least 30, sequences of genes selected from the group consisting with GenBank identification Nos. NM_003335; NM_000918; NM_006430.1; NM_001416.1; NM_004090; NM_006406.1; NM_003001.2; NM_001319; NM_006545.1; NM_021145.1; NM_002437.1; NM_006286; NM_001003698 /// NM_001003699 /// NM_002955; NM_001123 /// NM_006721; NM_024824; NM_004935.1; NM_002853.1; NM_019067.1; NM_024917.1; NM_020979.1; NM_005597.1; NM_007031.1; NM_009590.1; NM_020217.1; NM_025026.1; NM_014709.1; NM_014896.1; AF010144; NM_005374.1; NM_001696; NM_005494 /// NM_058246; NM_006534 /// NM_181659; NM_006368; NM_002268 /// NM_032771; NM_014033; NM_016138; NM_007048 /// NM_194441; NM_006694; NM_000051 /// NM _138292 /// NM_138293; NM_000410 /// NM_139002 /// NM_139003 /// NM_139004 /// NM_139005 /// NM_139006 /// NM_139007 /// NM_139008 /// NM_139009 /// NM_139010 /// NM_139011; NM_004691; NM_012070 /// NM_139321 /// NM_139322; NM_006095; AI632181; AW024467; NM_021814; NM_005547.1; NM_203458; NM_015547 /// NM_147161; AB007958.1; NM_207488; NM_005809 /// NM_181737 /// NM_181738; NM_016248 /// NM_144490; AK022213.1; NM_005708; NM_207102; AK023895; NM_144606 /// NM_144997; NM_018530; AK021474; U43604.1; AU147017; AF222691.1; NM_015116; NM_001005375 /// NM_001005785 /// NM_001005786 /// NM_004081 /// NM_020363 /// NM_020364 /// NM_020420; AC004692; NM_001014; NM_000585 /// NM_172174 /// NM_172175; NM_054020 /// NM_172095 /// NM_172096 /// NM_172097; BE466926; NM_018011; NM_024077; NM_012394; NM_019011 /// NM_207111 /// NM_207116; NM_017646; NM_021800; NM_016049; NM_014395; NM_014336; NM_018097; NM_019014; NM_024804; NM_018260; NM_018118; NM_014128; NM_024084; NM_005294; AF077053; NM_138387; NM_024531; NM_000693; NM_018509; NM_033128; NM_020706; AI523613; and NM_014884. 
     
     
         12 . The method of  claim 1 , wherein the gene group comprises sequences of genes selected from the group consisting of genes with GenBank identification Nos. NM_007062.1; NM_001281.1; BC000120.1; NM_014255.1; BC002642.1; NM_000346.1; NM_006545.1; BG034328; NM_021822.1; NM_021069.1; NM_019067.1; NM_017925.1; NM_017932.1; NM_030757.1; NM_030972.1; AF126181.1; U93240.1; U90552.1; AF151056.1; U85430.1; U51007.1; BC005969.1; NM_002271.1; AL566172; AB014576.1; BF218804; AK022494.1; AA114843; BE467941; NM_003541.1; R83000; AL161952.1; AK023843.1; AK021571.1; AK023783.1; AU147182; AL080112.1; AW971983; AI683552; NM_024006.1; AK026565.1; NM_014182.1; NM_021800.1; NM_016049.1; NM_019023.1; NM_021971.1; NM_014128.1; AK025651.1; AA133341; and AF198444.1. 
     
     
         13 . The method of  claim 1 , wherein the gene group comprises sequences of genes selected from the group consisting of genes with GenBank identification Nos. NM_007062.1; NM_001281.1; BC002642.1; NM_000346.1; NM_006545.1; BG034328; NM_019067.1; NM_017925.1; NM_017932.1; NM_030757.1; NM_030972.1; NM_002268 /// NM_032771; NM_007048 /// NM_194441; NM_006694; U85430.1; NM_004691; AB014576.1; BF218804; BE467941; R83000; AL161952.1; AK023843.1; AK021571.1; AK023783.1; AL080112.1; AW971983; AI683552; NM_024006.1; AK026565.1; NM_014182.1; NM_021800.1; NM_016049.1; NM_021971.1; NM_014128.1; AA133341; and AF198444.1 
     
     
         14 . The method of  claim 1 , wherein the group comprises sequences of genes selected from the group consisting of genes with GenBank or Unigene identification Nos. NM_030757.1; R83000; AK021571.1; NM_014182.1; NM_17932.1; U85430.1; AI683552; BC002642.1; AW024467; NM_030972.1; BC021135.1; AL161952.1; AK026565.1; AK023783.1; BF218804; NM_001281.1; NM_024006.1; AK023843.1; BC001602.1; BC034707.1; BC064619.1; AY280502.1; BC059387.1; AF135421.1; BC061522.1; L76200.1; U50532.1; BC006547.2; BC008797.2; BC000807.1; AL080112.1; BC033718.1 /// BC046176.1 /// BC038443.1; NM_000346.1; BC008710.1; Hs.288575 (UNIGENE ID); AF020591.1; BC000423.2; BC002503.2; BC008710.1; BC009185.2; Hs.528304 (UNIGENE ID); U50532.1; BC013923.2; BC031091; NM_007062; Hs.249591 (Unigene ID); BC075839.1 /// BC073760.1; BC072436.1 /// BC004560.2; BC001016.2; Hs.286261 (Unigene ID); AF348514.1; BC005023.1; BC066337.1 /// BC058736.1 /// BC050555.1; Hs.216623 (Unigene ID); BC072400.1; BC041073.1; U43965.1; BC021258.2; BC016057.1; BC016713.1 /// BC014535.1 /// AF237771.1; BC000360.2; BC007455.2; BC000701.2; BC010067.2; BC023528.2 /// BC047680.1; BC064957.1; Hs.156701 (Unigene ID); BC030619.2; BC008710.1; U43965.1; BC066329.1; Hs.438867 (Unigene ID); BC035025.2 /// BC050330.1; BC023976.2; BC074852.2 /// BC074851.2; Hs.445885 (Unigene ID); BC008591.2 /// BC050440.1 ///; BC048096.1; AF365931.1; AF257099.1; and BC028912.1. 
     
     
         15 . The method of  claim 1 , wherein the group comprises sequences of genes selected from the group consisting of genes with GenBank or Unigene identification Nos: NM_003335; NM_001319; NM_021145.1; NM_001003698 /// NM_001003699 ///; NM_002955; NM_002853.1; NM_019067.1; NM_024917.1; NM_020979.1; NM_005597.1; NM_007031.1; NM_009590.1; NM020217.1; NM_025026.1; NM_014709.1; NM_014896.1; AF010144; NM_005374.1; NM_006534 /// NM_181659; NM_014033; NM_016138; NM_007048 /// NM_194441; NM_000051 /// NM_138292 /// NM_138293; NM_000410 /// NM_139002 /// NM_139003 /// NM_139004 /// NM_139005 /// NM_139006 /// NM_139007 /// NM_139008 /// NM_139009 /// NM_139010 /// NM_139011; NM_012070 /// NM_139321 /// NM_139322; NM_006095; AI632181; AW024467; NM_021814; NM_005547.1; NM_203458; NM_015547 /// NM_147161; AB007958.1; NM_207488; NM_005809 /// NM_181737 /// NM_181738; NM_016248 /// NM_144490; AK022213.1; NM_005708; NM_207102; AK023895; NM_144606 /// NM_144997; NM_018530; AK021474; U43604.1; AU147017; AF222691.1; NM_015116; NM_001005375 /// NM_001005785 /// NM_001005786 /// NM_004081 /// NM_020363 /// NM_020364 /// NM_020420; AC004692; NM_001014; NM_000585 /// NM_172174 /// NM172175; NM_054020 /// NM_172095 /// NM_172096 /// NM_172097; BE466926; NM_018011; NM_024077; NM_019011 /// NM207111 /// NM207116; NM_017646; NM_014395; NM_014336; NM_018097; NM_019014; NM_024804; NM_018260; NM_018118; NM_014128; NM_024084; NM_005294; AF077053; NM_000693; NM_033128; NM_020706; AI523613; and NM_014884, and wherein decrease in expression of at least 5 of these genes is indicative of the individual being affected with a lung disease. 
     
     
         16 . The method of  claim 1 , wherein the group comprises sequences of genes selected from the group consisting of genes with GenBank or Unigene identification Nos NM_030757.1; R83000; AK021571.1; NM_17932.1; U85430.1; AI683552; BC002642.1; AW024467; NM_030972.1; BC021135.1; AL161952.1; AK026565.1; AK023783.1; BF218804; AK023843.1; BC001602.1; BC034707.1; BC064619.1; AY280502.1; BC059387.1; BC061522.1; U50532.1; BC006547.2; BC008797.2; BC000807.1; AL080112.1; BC033718.1 /// BC046176.1 ///; BC038443.1; Hs.288575 (UNIGENE ID); AF020591.1; BC002503.2; BC009185.2; Hs.528304 (UNIGENE ID); U50532.1; BC013923.2; BC031091; Hs.249591 (Unigene ID); Hs.286261 (Unigene ID); AF348514.1; BC066337.1 /// BC058736.1 /// BC050555.1; Hs.216623 (Unigene ID); BC072400.1; BC041073.1; U43965.1; BC021258.2; BC016057.1; BC016713.1 /// BC014535.1 /// AF237771.1; BC000701.2; BC010067.2; Hs.156701 (Unigene ID); BC030619.2; U43965.1; Hs.438867 (Unigene ID); BC035025.2 /// BC050330.1; BC074852.2 /// BC074851.2; Hs.445885 (Unigene ID); AF365931.1; and AF257099.1, and wherein decrease in expression of at least 5 of these genes is indicative of the individual being affected with a luncg disease. 
     
     
         17 . The method of  claim 1 , wherein the group comprises sequences of genes selected from the group consisting of genes with GenBank or Unigene identification Nos BF218804; AK022494.1; AA114843; BE467941; NM_003541.1; R83000; AL161952.1; AK023843.1; AK021571.1; AK023783.1; AU147182; AL080112.1; AW971983; AI683552; NM_024006.1; AK026565.1; NM_014182.1; NM_021800.1; NM_016049.1; NM_019023.1; NM_021971.1; NM_014128.1; AK025651.1; AA133341; and AF198444.1, and wherein decrease in expression of at least 5 of these genes is indicative of the individual being affected with a lung disease. 
     
     
         18 . The method of  claim 1 , wherein the group comprises sequences of genes selected from the group consisting of genes with GenBank or Unigene identification Nos NM_000918; NM_006430.1; NM_001416.1; NM_004090; NM_006406.1; NM_003001.2; NM_006545.1; NM_002437.1; NM_006286; NM_001123 /// NM_006721; NM_024824; NM_004935.1; NM_001696; NM_005494 /// NM_058246; NM_006368; NM_002268 /// NM _032771; NM_006694; NM_004691; NM_012394; NM_021800; NM_016049; NM_138387; NM_024531; and NM_018509, and wherein increase in expression of at least 5 of these genes is indicative of the individual being affected with a lung disease. 
     
     
         19 . The method of  claim 1 , wherein the group comprises sequences of genes selected from the group consisting of genes with GenBank or Unigene identification Nos NM_014182.1; NM_001281.1; NM_024006.1; AF135421.1; L76200.1; NM_000346.1; BC008710.1; BC000423.2; BC008710.1; NM_007062; BC075839.1 /// BC073760.1; BC072436.1 /// BC004560.2; BC001016.2; BC005023.1; BC000360.2; BC007455.2; BC023528.2 /// BC047680.1; BC064957.1; BC008710.1; BC066329.1; BC023976.2; BC008591.2 /// BC050440.1 /// BC048096.1; and BC028912.1, and wherein increase in expression of at least 5 of these genes is indicative of the individual being affected with a lung disease. 
     
     
         20 . The method of  claim 1 , wherein the group comprises sequences of genes selected from the group consisting of genes with GenBank or Unigene identification Nos NM_007062.1; NM_001281.1; BC000120.1; NM_014255.1; BC002642.1; NM_000346.1; NM_006545.1; BG034328; NM_021822.1; NM_021069.1; NM_019067.1; NM_017925.1; NM_017932.1; NM_030757.1; NM_030972.1; AF126181.1; U93240.1; U90552.1; AF151056.1; U85430.1; U51007.1; BC005969.1; NM_002271.1; AL566172; and AB014576.1, and wherein increase in expression of at least 5 of these genes is indicative of the individual being affected with a lung disease. 
     
     
         21 . The method of  claim 1 , wherein the group comprises 5-9 sequences of genes selected from group 1 and group 2, group 1 consisting of genes with GenBank or Unigene identification Nos. NM_003335; NM_001319; NM_021145.1; NM_001003698 /// NM_001003699 ///; NM_002955; NM_002853.1; NM_019067.1; NM_024917.1; NM_020979.1; NM_005597.1; NM_007031.1; NM_009590.1; NM_020217.1; NM_025026.1; NM_014709.1; NM_014896.1; AF010144; NM_005374.1; NM_006534 /// NM_181659; NM_014033; NM_016138; NM_007048 /// NM_194441; NM_000051 /// NM _138292 /// NM_138293; NM_000410 /// NM_139002 /// NM_139003 /// NM_139004 /// NM_139005 /// NM_139006 /// NM_139007 /// NM_139008 /// NM_139009 /// NM_139010 /// NM_139011; NM_012070 /// NM_139321 /// NM_139322; NM_006095; AI632181; AW024467; NM_021814; NM_005547.1; NM_203458; NM_015547 /// NM_147161; AB007958.1; NM_207488; NM_005809 /// NM_181737 /// NM_181738; NM_016248 /// NM_144490; AK022213.1; NM_005708; NM_207102; AK023895; NM_144606 /// NM_144997; NM_018530; AK021474; U43604.1; AU147017; AF222691.1; NM_015116; NM_001005375 /// NM_001005785 /// NM_001005786 /// NM_004081 /// NM_020363 /// NM_020364 /// NM_020420; AC004692; NM_001014; NM_000585 /// NM_172174 /// NM_172175; NM_054020 /// NM_172095 /// NM_172096 /// NM_172097; BE466926; NM_018011; NM_024077; NM_019011 /// NM_207111 /// NM_207116; NM_017646; NM_014395; NM_014336; NM_018097; NM_019014; NM_024804; NM_018260; NM_018118; NM_014128; NM_024084; NM_005294; AF077053; NM_000693; NM_033128; NM_020706; AI523613; and NM_014884, and group 2 consisting of genes with GenBank or Unigene identification Nos. NM_000918; NM_006430.1; NM_001416.1; NM_004090; NM_006406.1; NM_003001.2; NM_006545.1; NM_002437.1; NM_006286; NM_001123 /// NM_006721; NM_024824; NM_004935.1; NM_001696; NM_005494 /// NM_058246; NM_006368; NM_002268 /// NM_032771; NM_006694; NM_004691; NM_012394; NM_021800; NM_016049; NM_138387; NM_024531; and NM_018509, and a group of at least 20 genes selected from group 3 and group 4, group 3 consisting of genes with GenBank or Unigene identification Nos BF218804; AK022494.1; AA114843; BE467941; NM_003541.1; R83000; AL161952.1; AK023843.1; AK021571.1; AK023783.1; AU147182; AL080112.1; AW971983; AI683552; NM_024006.1; AK026565.1; NM_014182.1; NM_021800.1; NM_016049.1; NM_019023.1; NM_021971.1; NM_014128.1; AK025651.1; AA133341; and AF198444.1 and group 4 consisting of genes with GenBank or Unigene identification Nos. NM_007062.1; NM_001281.1; BC000120.1; NM_014255.1; BC002642.1; NM_000346.1; NM_006545.1; BG034328; NM_021822.1; NM_021069.1; NM_019067.1; NM_017925.1; NM_017932.1; NM_030757.1; NM_030972.1; AF126181.1; U93240.1; U90552.1; AF151056.1; U85430.1; U51007.1; BC005969.1; NM_002271.1; AL566172; and AB014576.1. 
     
     
         22 . The method of  claim 20 , wherein decrease in the expression of any one of the group 1 genes and increase in the expression of any one of the group 2 genes, and decrease of the group 3 genes and increase of the group 4 genes is indicative of the individual being affected with a lung disease. 
     
     
         23 . The method of  claim 1 , wherein the group comprises 5-9 sequences of genes selected from group 5 and group 6, group 5 consisting of genes with GenBank or Unigene identification Nos. NM_030757.1; R83000; AK021571.1; NM_17932.1; U85430.1; AI683552; BC002642.1; AW024467; NM_030972.1; BC021135.1; AL161952.1; AK026565.1; AK023783.1; BF218804; AK023843.1; BC001602.1; BC034707.1; BC064619.1; AY280502.1; BC059387.1; BC061522.1; U50532.1; BC006547.2; BC008797.2; BC000807.1; AL080112.1; BC033718.1 /// BC046176.1 ///; BC038443.1; Hs.288575 (UNIGENE ID); AF020591.1; BC002503.2; BC009185.2; Hs.528304 (UNIGENE ID); U50532.1; BC013923.2; BC031091; Hs.249591 (Unigene ID); Hs.286261 (Unigene ID); AF348514.1; BC066337.1 /// BC058736.1 /// BC050555.1; Hs.216623 (Unigene ID); BC072400.1; BC041073.1; U43965.1; BC021258.2; BC016057.1; BC016713.1 /// BC014535.1 /// AF237771.1; BC000701.2; BC010067.2; Hs.156701 (Unigene ID); BC030619.2; U43965.1; Hs.438867 (Unigene ID); BC035025.2 /// BC050330.1; BC074852.2 /// BC074851.2; Hs.445885 (Unigene ID); AF365931.1; and AF257099.1, and group 6 consisting of genes with GenBank or Unigene identification Nos. NM_014182.1; NM_001281.1; NM_024006.1; AF135421.1; L76200.1; NM_000346.1; BC008710.1; BC000423.2; BC008710.1; NM_007062; BC075839.1 /// BC073760.1; BC072436.1 /// BC004560.2; BC001016.2; BC005023.1; BC000360.2; BC007455.2; BC023528.2 /// BC047680.1; BC064957.1; BC008710.1; BC066329.1; BC023976.2; BC008591.2 /// BC050440.1 ///; BC048096.1; and BC028912.1, and a group of at least 20 genes selected from group 3 and group 4, group 3 consisting of genes with GenBank or Unigene identification Nos BF218804; AK022494.1; AA114843; BE467941; NM_003541.1; R83000; AL161952.1; AK023843.1; AK021571.1; AK023783.1; AU147182; AL080112.1; AW971983; AI683552; NM_024006.1; AK026565.1; NM_014182.1; NM_021800.1; NM_016049.1; NM_019023.1; NM_021971.1; NM_014128.1; AK025651.1; AA133341; and AF198444.1 and group 4 consisting of genes with GenBank or Unigene identification Nos. NM_007062.1; NM_001281.1; BC000120.1; NM_014255.1; BC002642.1; NM_000346.1; NM_006545.1; BG034328; NM_021822.1; NM_021069.1; NM_019067.1; NM_017925.1; NM_017932.1; NM_030757.1; NM_030972.1; AF126181.1; U93240.1; U90552.1; AF151056.1; U85430.1; U51007.1; BC005969.1; NM_002271.1; AL566172; and AB014576.1, wherein decrease in the expression of the group 5 genes and increase in the expression of the group 6 genes, and decrease the group 3 genes and increase of the group 4 genes is indicative of the individual being affected with a lung disease.