Lung Cancer Biomarkers and Uses Thereof

Abstract

The present application includes biomarkers, methods, devices, reagents, systems, and kits for the detection and diagnosis of lung cancer. In one aspect, the application provides biomarkers that can be used alone or in various combinations to diagnose lung cancer or permit the differential diagnosis of pulmonary nodules as benign or malignant. In another aspect, methods are provided for diagnosing lung cancer in an individual, where the methods include detecting, in a biological sample from an individual, at least one biomarker value corresponding to at least one biomarker selected from the group of biomarkers provided in Table 18, Table 20, or Table 21, wherein the individual is classified as having lung cancer, or the likelihood of the individual having lung cancer is determined, based on the at least one biomarker value.

What is claimed is: 
     
         1 . A method for diagnosing that an individual does or does not have lung cancer, the method comprising:
 detecting, in a biological sample from an individual, biomarker values that each correspond to one of at least N biomarkers selected from Table 21, wherein said individual is classified as having or not having lung cancer based on said biomarker values, and wherein N=2-86.   
     
     
         2 . The method of  claim 1 , wherein detecting the biomarker values comprises performing an in vitro assay. 
     
     
         3 . The method of  claim 2 , wherein said in vitro assay comprises at least one capture reagent corresponding to each of said biomarkers, and further comprising selecting said at least one capture reagent from the group consisting of aptamers, antibodies, and a nucleic acid probe. 
     
     
         4 . The method of  claim 3 , wherein said at least one capture reagent is an aptamer. 
     
     
         5 . The method of  claim 2 , wherein the in vitro assay is selected from the group consisting of an immunoassay, an aptamer-based assay, a histological or cytological assay, and an mRNA expression level assay. 
     
     
         6 . The method of  claim 1 , wherein each biomarker value is evaluated based on a predetermined value or a predetermined range of values. 
     
     
         7 . The method  claim 1 , wherein the biological sample is lung tissue and wherein the biomarker values derive from a histological or cytological analysis of said lung tissue. 
     
     
         8 . The method of  claim 1 , wherein the biological sample is selected from the group consisting of whole blood, plasma, and serum. 
     
     
         9 . The method of  claim 1 , wherein the biological sample is serum. 
     
     
         10 . The method of  claim 1 , wherein the individual is a human. 
     
     
         11 . The method of  claim 1 , wherein N=2-15. 
     
     
         12 . The method of  claim 1 , wherein N=2-10. 
     
     
         13 . The method of  claim 1 , wherein N=3-10. 
     
     
         14 . The method of  claim 1 , wherein N=4-10. 
     
     
         15 . The method of  claim 1 , wherein N=5-10. 
     
     
         16 . The method of  claim 1 , wherein the individual is a smoker. 
     
     
         17 . The method of  claim 1 , wherein the individual has a pulmonary nodule. 
     
     
         18 . The method of  claim 1 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         19 . A computer-implemented method for indicating a likelihood of lung cancer, the method comprising:
 retrieving on a computer biomarker information for an individual, wherein the biomarker information comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 21;   performing with the computer a classification of each of said biomarker values; and   indicating a likelihood that said individual has lung cancer based upon a plurality of classifications, and wherein N=2-86.   
     
     
         20 . The method of  claim 19 , wherein indicating the likelihood that the individual has lung cancer comprises displaying the likelihood on a computer display. 
     
     
         21 . A computer program product for indicating a likelihood of lung cancer, the computer program product comprising:
 a computer readable medium embodying program code executable by a processor of a computing device or system, the program code comprising:   code that retrieves data attributed to a biological sample from an individual, wherein the data comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 21, wherein said biomarkers were detected in the biological sample; and   code that executes a classification method that indicates a lung disease status of the individual as a function of said biomarker values; and wherein N=2-86.   
     
     
         22 . The computer program product of  claim 21 , wherein said classification method uses a probability density function. 
     
     
         23 . The computer program product of  claim 22 , wherein said classification method uses two or more classes. 
     
     
         24 . A method for diagnosing that an individual does or does not have lung cancer, the method comprising:
 detecting, in a biological sample from an individual, biomarker values that each correspond to one of at least N biomarkers selected from Table 20, wherein said individual is classified as having or not having lung cancer based on said biomarker values, and wherein N=2-25.   
     
     
         25 . The method of  claim 24 , wherein detecting the biomarker values comprises performing an in vitro assay. 
     
     
         26 . The method of  claim 25 , wherein said in vitro assay comprises at least one capture reagent corresponding to each of said biomarkers, and further comprising selecting said at least one capture reagent from the group consisting of aptamers, antibodies, and a nucleic acid probe. 
     
     
         27 . The method of  claim 26 , wherein said at least one capture reagent is an aptamer. 
     
     
         28 . The method of  claim 25 , wherein the in vitro assay is selected from the group consisting of an immunoassay, an aptamer-based assay, a histological or cytological assay, and an mRNA expression level assay. 
     
     
         29 . The method of  claim 24 , wherein each biomarker value is evaluated based on a predetermined value or a predetermined range of values. 
     
     
         30 . The method  claim 24 , wherein the biological sample is lung tissue and wherein the biomarker values derive from a histological or cytological analysis of said lung tissue. 
     
     
         31 . The method of  claim 24 , wherein the biological sample is selected from the group consisting of whole blood, plasma, and serum. 
     
     
         32 . The method of  claim 24 , wherein the biological sample is serum. 
     
     
         33 . The method of  claim 24 , wherein the individual is a human. 
     
     
         34 . The method of  claim 24 , wherein N=2-15. 
     
     
         35 . The method of  claim 24 , wherein N=2-10. 
     
     
         36 . The method of  claim 24 , wherein N=3-10. 
     
     
         37 . The method of  claim 24 , wherein N=4-10. 
     
     
         38 . The method of  claim 24 , wherein N=5-10. 
     
     
         39 . The method of  claim 24 , wherein the individual is a smoker. 
     
     
         40 . The method of  claim 24 , wherein the individual has a pulmonary nodule. 
     
     
         41 . The method of  claim 24 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         42 . A computer-implemented method for indicating a likelihood of lung cancer, the method comprising:
 retrieving on a computer biomarker information for an individual, wherein the biomarker information comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 20;   performing with the computer a classification of each of said biomarker values; and   indicating a likelihood that said individual has lung cancer based upon a plurality of classifications, and wherein N=2-25.   
     
     
         43 . The method of  claim 42 , wherein indicating the likelihood that the individual has lung cancer comprises displaying the likelihood on a computer display. 
     
     
         44 . A computer program product for indicating a likelihood of lung cancer, the computer program product comprising:
 a computer readable medium embodying program code executable by a processor of a computing device or system, the program code comprising:   code that retrieves data attributed to a biological sample from an individual, wherein the data comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 20, wherein said biomarkers were detected in the biological sample; and   code that executes a classification method that indicates a lung disease status of the individual as a function of said biomarker values; and wherein N=2-25.   
     
     
         45 . The computer program product of  claim 44 , wherein said classification method uses a probability density function. 
     
     
         46 . The computer program product of  claim 44 , wherein said classification method uses two or more classes. 
     
     
         47 . A method for diagnosing that an individual does or does not have lung cancer, the method comprising:
 detecting, in a biological sample from an individual, biomarker values that each correspond to one of at least N biomarkers selected from Table 18, wherein said individual is classified as having or not having lung cancer based on said biomarker values, and wherein N=2-36.   
     
     
         48 . The method of  claim 47 , wherein detecting the biomarker values comprises performing an in vitro assay. 
     
     
         49 . The method of  claim 48 , wherein said in vitro assay comprises at least one capture reagent corresponding to each of said biomarkers, and further comprising selecting said at least one capture reagent from the group consisting of aptamers, antibodies, and a nucleic acid probe. 
     
     
         50 . The method of  claim 49 , wherein said at least one capture reagent is an aptamer. 
     
     
         51 . The method of  claim 48 , wherein the in vitro assay is selected from the group consisting of an immunoassay, an aptamer-based assay, a histological or cytological assay, and an mRNA expression level assay. 
     
     
         52 . The method of  claim 47 , wherein each biomarker value is evaluated based on a predetermined value or a predetermined range of values. 
     
     
         53 . The method  claim 47 , wherein the biological sample is lung tissue and wherein the biomarker values derive from a histological or cytological analysis of said lung tissue. 
     
     
         54 . The method of  claim 47 , wherein the biological sample is selected from the group consisting of whole blood, plasma, and serum. 
     
     
         55 . The method of  claim 47 , wherein the biological sample is serum. 
     
     
         56 . The method of  claim 47 , wherein the individual is a human. 
     
     
         57 . The method of  claim 47 , wherein N=2-15. 
     
     
         58 . The method of  claim 47 , wherein N=2-10. 
     
     
         59 . The method of  claim 47 , wherein N=3-10. 
     
     
         60 . The method of  claim 47 , wherein N=4-10. 
     
     
         61 . The method of  claim 47 , wherein N=5-10. 
     
     
         62 . The method of  claim 47 , wherein the individual is a smoker. 
     
     
         63 . The method of  claim 47 , wherein the individual has a pulmonary nodule. 
     
     
         64 . The method of  claim 47 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         65 . A computer-implemented method for indicating a likelihood of lung cancer, the method comprising:
 retrieving on a computer biomarker information for an individual, wherein the biomarker information comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 18;   performing with the computer a classification of each of said biomarker values; and   indicating a likelihood that said individual has lung cancer based upon a plurality of classifications, and wherein N=2-36.   
     
     
         66 . The method of  claim 65 , wherein indicating the likelihood that the individual has lung cancer comprises displaying the likelihood on a computer display. 
     
     
         67 . A computer program product for indicating a likelihood of lung cancer, the computer program product comprising:
 a computer readable medium embodying program code executable by a processor of a computing device or system, the program code comprising:   code that retrieves data attributed to a biological sample from an individual, wherein the data comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 18, wherein said biomarkers were detected in the biological sample; and   code that executes a classification method that indicates a lung disease status of the individual as a function of said biomarker values; and wherein N=2-36.   
     
     
         68 . The computer program product of  claim 67 , wherein said classification method uses a probability density function. 
     
     
         69 . The computer program product of  claim 68 , wherein said classification method uses two or more classes. 
     
     
         70 . A method for determining information about lung cancer in an individual comprising:
 detecting, in a biological sample from an individual, biomarker values that each correspond to one of at least N biomarkers selected from Table 21, wherein N=2-86; and wherein said biomarker value provides information about the lung cancer in the individual.   
     
     
         71 . The method of  claim 70 , wherein detecting the biomarker values comprises performing an in vitro assay. 
     
     
         72 . The method of  claim 71 , wherein said in vitro assay comprises at least one capture reagent corresponding to each of said biomarkers, and further comprising selecting said at least one capture reagent from the group consisting of aptamers, antibodies, and a nucleic acid probe. 
     
     
         73 . The method of  claim 72 , wherein said at least one capture reagent is an aptamer. 
     
     
         74 . The method of  claim 71 , wherein the in vitro assay is selected from the group consisting of an immunoassay, an aptamer-based assay, a histological or cytological assay, and an mRNA expression level assay. 
     
     
         75 . The method of  claim 70 , wherein each biomarker value is evaluated based on a predetermined value or a predetermined range of values. 
     
     
         76 . The method  claim 70 , wherein the biological sample is lung tissue and wherein the biomarker values derive from a histological or cytological analysis of said lung tissue. 
     
     
         77 . The method of  claim 70 , wherein the biological sample is selected from the group consisting of whole blood, plasma, and serum. 
     
     
         78 . The method of  claim 70 , wherein the biological sample is serum. 
     
     
         79 . The method of  claim 70 , wherein the individual is a human. 
     
     
         80 . The method of  claim 70 , wherein N=2-15. 
     
     
         81 . The method of  claim 70 , wherein N=2-10. 
     
     
         82 . The method of  claim 70 , wherein N=3-10. 
     
     
         83 . The method of  claim 70 , wherein N=4-10. 
     
     
         84 . The method of  claim 70 , wherein N=5-10. 
     
     
         85 . The method of  claim 70 , wherein the individual is a smoker. 
     
     
         86 . The method of  claim 70 , wherein the individual has a pulmonary nodule. 
     
     
         87 . The method of  claim 70 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         88 . The method of  claim 70 , wherein the information comprises prognosis, cancer classification, prediction of disease risk, or selection of treatment. 
     
     
         89 . A method for determining information about lung cancer in an individual comprising:
 detecting, in a biological sample from an individual, biomarker values that each correspond to one of at least N biomarkers selected from Table 18, wherein N=2-36; and wherein said biomarker value provides information about the lung cancer in the individual.   
     
     
         90 . The method of  claim 89 , wherein detecting the biomarker values comprises performing an in vitro assay. 
     
     
         91 . The method of  claim 90 , wherein said in vitro assay comprises at least one capture reagent corresponding to each of said biomarkers, and further comprising selecting said at least one capture reagent from the group consisting of aptamers, antibodies, and a nucleic acid probe. 
     
     
         92 . The method of  claim 91 , wherein said at least one capture reagent is an aptamer. 
     
     
         93 . The method of  claim 90 , wherein the in vitro assay is selected from the group consisting of an immunoassay, an aptamer-based assay, a histological or cytological assay, and an mRNA expression level assay. 
     
     
         94 . The method of  claim 89 , wherein each biomarker value is evaluated based on a predetermined value or a predetermined range of values. 
     
     
         95 . The method  claim 89 , wherein the biological sample is lung tissue and wherein the biomarker values derive from a histological or cytological analysis of said lung tissue. 
     
     
         96 . The method of  claim 89 , wherein the biological sample is selected from the group consisting of whole blood, plasma, and serum. 
     
     
         97 . The method of  claim 89 , wherein the biological sample is serum. 
     
     
         98 . The method of  claim 89 , wherein the individual is a human. 
     
     
         99 . The method of  claim 89 , wherein N=2-15. 
     
     
         100 . The method of  claim 89 , wherein N=2-10. 
     
     
         101 . The method of  claim 89 , wherein N=3-10. 
     
     
         102 . The method of  claim 89 , wherein N=4-10. 
     
     
         103 . The method of  claim 89 , wherein N=5-10. 
     
     
         104 . The method of  claim 89 , wherein the individual is a smoker. 
     
     
         105 . The method of  claim 89 , wherein the individual has a pulmonary nodule. 
     
     
         106 . The method of  claim 89 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         107 . The method of  claim 89 , wherein the information comprises prognosis, cancer classification, prediction of disease risk, or selection of treatment. 
     
     
         108 . A method for determining information about lung cancer in an individual comprising:
 detecting, in a biological sample from an individual, biomarker values that each correspond to one of at least N biomarkers selected from Table 20, wherein N=2-25; and wherein said biomarker value provides information about the lung cancer in the individual.   
     
     
         109 . The method of  claim 108 , wherein detecting the biomarker values comprises performing an in vitro assay. 
     
     
         110 . The method of  claim 109 , wherein said in vitro assay comprises at least one capture reagent corresponding to each of said biomarkers, and further comprising selecting said at least one capture reagent from the group consisting of aptamers, antibodies, and a nucleic acid probe. 
     
     
         111 . The method of  claim 110 , wherein said at least one capture reagent is an aptamer. 
     
     
         112 . The method of  claim 109 , wherein the in vitro assay is selected from the group consisting of an immunoassay, an aptamer-based assay, a histological or cytological assay, and an mRNA expression level assay. 
     
     
         113 . The method of  claim 108 , wherein each biomarker value is evaluated based on a predetermined value or a predetermined range of values. 
     
     
         114 . The method  claim 108 , wherein the biological sample is lung tissue and wherein the biomarker values derive from a histological or cytological analysis of said lung tissue. 
     
     
         115 . The method of  claim 108 , wherein the biological sample is selected from the group consisting of whole blood, plasma, and serum. 
     
     
         116 . The method of  claim 108 , wherein the biological sample is serum. 
     
     
         117 . The method of  claim 108 , wherein the individual is a human. 
     
     
         118 . The method of  claim 108 , wherein N=2-15. 
     
     
         119 . The method of  claim 108 , wherein N=2-10. 
     
     
         120 . The method of  claim 108 , wherein N=3-10. 
     
     
         121 . The method of  claim 108 , wherein N=4-10. 
     
     
         122 . The method of  claim 108 , wherein N=5-10. 
     
     
         123 . The method of  claim 108 , wherein the individual is a smoker. 
     
     
         124 . The method of  claim 108 , wherein the individual has a pulmonary nodule. 
     
     
         125 . The method of  claim 108 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         126 . The method of  claim 108 , wherein the information comprises prognosis, cancer classification, prediction of disease risk, or selection of treatment. 
     
     
         127 . A method for diagnosing that an individual does or does not have lung cancer, the method comprising:
 detecting, in a biological sample from an individual, biomarker values that each correspond to one of at least N biomarkers selected from Table 21, wherein said individual is classified as having or not having lung cancer based on said biomarker values, wherein N=2-86, and wherein at least one of said biomarkers is selected from Table 20.   
     
     
         128 . The method of  claim 127 , wherein at least one of said biomarkers selected from Table 20 is MMP-12. 
     
     
         129 . The method of  claim 127 , wherein detecting the biomarker values comprises performing an in vitro assay. 
     
     
         130 . The method of  claim 129 , wherein said in vitro assay comprises at least one capture reagent corresponding to each of said biomarkers, and further comprising selecting said at least one capture reagent from the group consisting of aptamers, antibodies, and a nucleic acid probe. 
     
     
         131 . The method of  claim 130 , wherein said at least one capture reagent is an aptamer. 
     
     
         132 . The method of  claim 129 , wherein the in vitro assay is selected from the group consisting of an immunoassay, an aptamer-based assay, a histological or cytological assay, and an mRNA expression level assay. 
     
     
         133 . The method of  claim 127 , wherein each biomarker value is evaluated based on a predetermined value or a predetermined range of values. 
     
     
         134 . The method  claim 127 , wherein the biological sample is lung tissue and wherein the biomarker values derive from a histological or cytological analysis of said lung tissue. 
     
     
         135 . The method of  claim 127 , wherein the biological sample is selected from the group consisting of whole blood, plasma, and serum. 
     
     
         136 . The method of  claim 127 , wherein the biological sample is serum. 
     
     
         137 . The method of  claim 127 , wherein the individual is a human. 
     
     
         138 . The method of  claim 127 , wherein N=2-15. 
     
     
         139 . The method of  claim 127 , wherein N=2-10. 
     
     
         140 . The method of  claim 127 , wherein N=3-10. 
     
     
         141 . The method of  claim 127 , wherein N=4-10. 
     
     
         142 . The method of  claim 127 , wherein N=5-10. 
     
     
         143 . The method of  claim 127 , wherein the individual is a smoker. 
     
     
         144 . The method of  claim 127 , wherein the individual has a pulmonary nodule. 
     
     
         145 . The method of  claim 127 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         146 . A computer-implemented method for indicating a likelihood of lung cancer, the method comprising:
 retrieving on a computer biomarker information for an individual, wherein the biomarker information comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 21; wherein at least one of said N biomarkers is selected from Table 20   performing with the computer a classification of each of said biomarker values; and   indicating a likelihood that said individual has lung cancer based upon a plurality of classifications, and wherein N=2-86.   
     
     
         147 . The method of  claim 146  wherein at least one of said biomarker(s) selected from Table 20 is MMP-12. 
     
     
         148 . The method of  claim 146 , wherein indicating the likelihood that the individual has lung cancer comprises displaying the likelihood on a computer display. 
     
     
         149 . A computer program product for indicating a likelihood of lung cancer, the computer program product comprising:
 a computer readable medium embodying program code executable by a processor of a computing device or system, the program code comprising:   code that retrieves data attributed to a biological sample from an individual, wherein the data comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 21, wherein at least one of said N biomarkers is selected from Table 10, and wherein said biomarkers were detected in the biological sample; and   code that executes a classification method that indicates a lung disease status of the individual as a function of said biomarker values; and wherein N=2-86.   
     
     
         150 . The computer program product of  claim 149 , wherein at least one of said biomarker(s) selected from Table 20 is MMP-12. 
     
     
         151 . The computer program product of  claim 149 , wherein said classification method uses a probability density function. 
     
     
         152 . The computer program product of  claim 149 , wherein said classification method uses two or more classes.