Lung cancer biomarkers

Abstract

The present invention relates to methods of diagnosing lung cancer in a patient, as well as methods of monitoring the progression of lung cancer and/or methods of monitoring a treatment protocol of a therapeutic agent or a therapeutic regimen. The invention also relates to assay methods used in connection with the diagnostic methods described herein.

1 - 53 . (canceled) 
     
     
         54 . A method for evaluating the efficacy of a treatment regimen in a patient diagnosed with lung cancer, said method comprising
 (a) obtaining a test sample from a patient undergoing said treatment regimen for lung cancer;   (b) measuring a level of a biomarker in said test sample, wherein said biomarker comprises MDC, NME-2, KGF, PlGF, Flt-3L, HGF, MCP1, SAT-1, MIP-1-b, GCLM, OPG, TNF RII, VEGF-D, ITAC, MMP-10, GPI, PPP2R4, AKR1B1, Amy1A, MIP-1b, P-Cadherin, EPO, MMP-2, EGFR, MMP-3, ErbB2, cytokeratin-19, E-cadherin, IL-6, osteopontin, cKit, uPA, NSE, cMET, MDC, Flt-1, CEA, cytokeratin-8, KGF, S100A6, IL2-R, and combinations thereof, and a set of labeled detection antibodies specific for said human analytes;   (c) comparing said level to a normal control level of said biomarker; and   (d) evaluating from said comparing step (c) whether said patient is responsive to said treatment regimen.   
     
     
         55 . The method of  claim 54  wherein said measuring step comprises conducting a multiplexed assay measurement of a plurality of said biomarkers in said test sample, wherein said multiplexed assay measurement is conducted using one reaction volume comprising said test sample. 
     
     
         56 . The method of  claim 54  wherein said measuring step(s) are conducted on a single sample. 
     
     
         57 . The method of  claim 54  wherein said measuring step(s) are conducted in a single assay chamber. 
     
     
         58 . The method of  claim 57  wherein said assay chamber is a single well of an assay plate. 
     
     
         59 . The method of  claim 57  wherein said assay chamber is a cartridge. 
     
     
         60 . The method of  claim 54  wherein said sample is selected from the group consisting of blood, peripheral blood mononuclear cells (PBMC), isolated blood cells, urine, serum and plasma. 
     
     
         61 . The method of  claim 54  wherein said sample is selected from serum or plasma. 
     
     
         62 . The method of  claim 54  wherein said sample is serum. 
     
     
         63 . The method of  claim 54  wherein said sample is plasma. 
     
     
         64 . The method of  claim 54  wherein said level(s) are measured using an immunoassay. 
     
     
         65 . The method of  claim 54  wherein said biomarkers comprise Flt-3L, EGFR, MMP-3, and NME-2 and combinations thereof. 
     
     
         66 . The method of  claim 54 , wherein the measurement step is conducted with one or more vials, containers, or compartments, containing a set of calibrator proteins. 
     
     
         67 . The method of  claim 54 , wherein said detection antibodies are labeled with an electrochemiluminescent (ECL) label. 
     
     
         68 . The method of  claim 54 , wherein the measuring step measures the level of the analytes in serum with a Receiver Operating Characteristic (ROC) area of 0.91, and the comparison step comprises a clinical sensitivity of 88% and a clinical specificity of 82% compared to the level in heavy smokers. 
     
     
         69 . The method of  claim 54 , wherein the measurement step comprises measurement with at least four discrete binding domains, which are in the form of a spot pattern. 
     
     
         70 . The method of  claim 69 , wherein the spot pattern meets the following specifications: Δx<0.2 mm, Δy<0.2 mm, and α<0.1°, wherein (a) Δx is the difference between a center of the spot pattern and a center of a well along the x axis of the plate; (b) Δy is the difference between the center of a spot pattern and a center of the well along the y axis of the plate; and (c) α is a counter-clockwise angle between the x axis of the plate bottom and the x axis of the plate top.