Biomarkers in Peripheral Blood Mononuclear Cells for Diagnosing or Detecting Lung Cancers

Abstract

Methods and compositions are provided for diagnosing or detecting a condition, e.g., lung disease in a mammalian subject by use of a micro-RNA expression level or an expression level profile of multiple miRNA in the peripheral blood mononuclear cells (PBMC) of the subject which is characteristic of COPD or NSCLC. Detection of changes in expression in specific miRNA biomarkers from that of a reference sample or miRNA expression profile are correlated with non-small cell lung cancer (NSCLC) and/or COPD and permit differentiation among healthy subjects, subjects with COPD and subjects with adenocarcinoma or squamous cell carcinoma.

1 . A method for monitoring or detecting lung disease in a subject who has undergone surgical resection of a non-small cell lung cancer (NSCLC) tumor comprising:
 (a) obtaining a biological sample from the subject;   (b) detecting in the biological sample the expression level of one more miRNAs selected from the group consisting of miR-let-7c, miR-34a, hsa-miR-202*, and miR-769-5p, and miR-642   (c) comparing the miRNA expression level in the biological sample to a reference miRNA standard,   wherein the expression level of said one or more miRNAs relative to the miRNA standard indicates the presence of a NSCLC.   
     
     
         2 . The method according to  claim 1 , wherein the NSCLC is squamous cell carcinoma or adenocarcinoma. 
     
     
         3 . The method according to  claim 1 , wherein the biological sample is whole blood, peripheral blood mononuclear cells, plasma, or serum. 
     
     
         4 . The method according to  claim 1 , wherein the reference miRNA standard is a reference subject or reference population selected from the group consisting of
 (a) a reference human subject or population having a NSCLC;   (b) a reference human subject or population having COPD;   (c) a reference human subject or population who are healthy and have never smoked;   (d) a reference human subject or population who are former smokers or current smokers with no disease;   (e) a reference human subject or population having benign lung nodules;   (f) a reference human subject or population following surgical removal of a NSCLC tumor;   (g) a reference human subject or population prior to surgical removal of a NSCLC tumor; and   (h) the same subject who provided a temporally earlier biological sample.   
     
     
         5 . The method according to  claim 1 , wherein the reference miRNA standard is a mean, an average, a numerical mean or range of numerical means, a numerical pattern, a graphical pattern or a miRNA expression profile derived from a reference subject or reference population. 
     
     
         6 . The method according to  claim 1 , further comprising detecting one or more miRNA selected from the group consisting of miR-148a, miR-142-5p, miR-221, miR-let-7d, miR-let-7a, and miR-328. 
     
     
         7 . The method according to  claim 1 , further comprising treating the NSCLC. 
     
     
         8 . The method according to  claim 1 , wherein the detecting step further comprises contacting the biological sample from the subject with a diagnostic reagent that measures the miRNA expression level in the sample. 
     
     
         9 . A method for monitoring or detecting lung disease in a subject who has undergone surgical resection of a non-small cell lung cancer (NSCLC) tumor tissue comprising:
 (a) obtaining a first biological sample from the subject before surgical resection of NSCLC tumor tissue;   (b) obtaining a second biological sample from the subject after surgical resection of NSCLC tumor tissue;   (c) measuring the expression of level of one more miRNAs selected from the group consisting of miR-let-7c, miR-34a, hsa-miR-202*, and miR-769-5p, and miR-642 in said first and second samples; and   (d) identifying a patient who has undergone successful tumor resection where the miRNA level is reduced in said second sample relative to said first sample,   wherein said first and second biological samples are selected from whole blood, peripheral blood mononuclear cells, plasma, and serum.