Lung Cancer Biomarkers and Uses Thereof

Abstract

The present disclosure includes biomarkers, methods, devices, reagents, systems, and kits for the detection and diagnosis of non-small cell lung cancer and general cancer. In one aspect, methods are provided for diagnosing non-small cell lung cancer, where the methods include detecting, in a sample, at least one biomarker value corresponding to at least one biomarker selected from the biomarkers provided in Table 1, wherein an individual is classified as having lung cancer, or the likelihood of having lung cancer is determined, based on the at least one biomarker value. In another aspect, methods are provided for diagnosing cancer, where the methods include detecting, in a sample, at least one biomarker value corresponding to at least one biomarker selected from the biomarkers provided in Table 19, wherein an individual is classified as having cancer, or the likelihood of having cancer is determined, based on the at least one biomarker value.

1 . A method for diagnosing that an individual does or does not have non-small cell lung cancer (NSCLC), the method comprising:
 providing a biomarker panel comprising N of the biomarker proteins listed in Table 1; wherein N is an integer from 2 to 59; and   detecting biomarker proteins, in a biological sample from an individual, to give biomarker values that each correspond to one of said N biomarker proteins in the panel, wherein said individual is classified as having or not having lung cancer based on said biomarker values.   
     
     
         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 an individual is classified as having ovarian cancer, or the likelihood of the individual having ovarian cancer is determined, based on a classification score that deviates from on a predetermined threshold. 
     
     
         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 to 15. 
     
     
         12 . The method of  claim 1 , wherein N=2 to 10. 
     
     
         13 . The method of  claim 1 , wherein N=3 to 10. 
     
     
         14 . The method of  claim 1 , wherein N=4 to 10. 
     
     
         15 . The method of  claim 1 , wherein N=5 to 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 biomarkers are selected from Table 13. 
     
     
         19 . A computer-implemented method for indicating a likelihood of NSCLC, 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 1;   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=2-59.   
     
     
         20 - 23 . (canceled) 
     
     
         24 . A method for screening an asymptomatic high risk individual for NSCL, the method comprising:
 providing a biomarker panel comprising N of the biomarker proteins listed in Table 1; wherein N is an integer from 2 to 59; and   detecting biomarker proteins, in a biological sample from an individual, to give biomarker values that each correspond to one of said N biomarkers proteins in the panel, wherein said individual is classified as having or not having NSCLC, or the likelihood of the individual having NSCLC is determined, based on said biomarker values.   
     
     
         25 - 41 . (canceled) 
     
     
         42 . A method for diagnosing that an individual does or does not have NSCLC, the method comprising:
 providing a biomarker panel comprising N of the biomarker proteins listed in Table 1; and   detecting, in a biological sample from an individual, biomarker values that each correspond to one of said N biomarker proteins in the panel, wherein the biomarker panel has a AUC value of 0.80 or greater.   
     
     
         43 . (canceled) 
     
     
         45 . A method for diagnosing that an individual does or does not have cancer, the method comprising:
 providing a biomarker panel comprising N of the biomarker proteins listed in Table 19; wherein N is an integer from 3 to 23; and   detecting biomarker proteins, in a biological sample from an individual, to give biomarker values that each correspond to one of said N biomarker proteins in the panel, wherein said individual is classified as having or not having cancer based on said biomarker values.   
     
     
         46 - 56 . (canceled) 
     
     
         57 . A computer-implemented method for indicating a likelihood of 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 19;   performing with the computer a classification of each of said biomarker values; and   indicating a likelihood that said individual has cancer based upon a plurality of classifications, and wherein N=3-3.   
     
     
         58 - 61 . (canceled) 
     
     
         62 . The method according to  claim 1 , wherein said individual is classified as having or not having NSCLC, or the likelihood of the individual having NSCLC is determined, based on said biomarker values and at least one item of additional biomedical information corresponding to said individual. 
     
     
         63 . (canceled) 
     
     
         64 . The method according to  claim 62 , wherein said at least one item of additional biomedical information is independently selected from the group consisting of:
 (a) information corresponding to physical descriptors of said individual,   (b) information corresponding to the radiologic descriptors of a pulmonary abnormality in said individual,   (c) information corresponding to the presence or absence of a pulmonary nodule in said individual,   (d) information corresponding to physical descriptors of a pulmonary nodule in said individual,   (e) information corresponding to a change in height and/or weight of said individual,   (f) information corresponding to the ethnicity of said individual,   (g) information corresponding to the gender of said individual,   (h) information corresponding the smoking history of said individual,   (i) information corresponding to environmental tobacco exposure in said individual,   (j) information corresponding to alcohol use history in said individual,   (k) information corresponding to occupational history of said individual,   (l) information corresponding to family history of lung cancer or other cancer in said individual,   (m) information corresponding to the presence or absence in said individual of at least one genetic marker correlating with a higher risk of lung cancer or cancer in said individual or a family member of said individual,   (n) information corresponding to clinical symptoms of said individual,   (o) information corresponding to other laboratory tests,   (p) information corresponding to gene expression values of said individual, and   (q) information corresponding to said individual's exposure to known carcinogens.   
     
     
         65 . A classifier comprising the biomarkers of Table 13. 
     
     
         66 . A classifier comprising the biomarkers in Example 5, specifically MMP12, MMP7, KLK3-SERPINA3, CRP, C9, CNDP1, and EGFR.