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 non-transitory computer readable medium having stored thereon a computer program which, when executed by a computer system operably connected to an assay kit configured to evaluate the efficacy of a treatment regimen in a patient diagnosed with kidney disease, causes the computer system to perform a method of monitoring kidney health in a patient comprising:
 (a) receiving a measurement of a level of a plurality of biomarkers in a test sample from a patient, wherein the plurality of biomarkers is selected from MDC, NME-2, KGF, P1GF, Flt-3L, HGF, MCP1, SAT-1, MIP-1-b, GCLM, OPG, TNF RH, VEGF-D, ITAC, MMP-10, GPI, PPP2R4, AKR1B1, Amy1A, MIP-1b, P-Cadherin, IP-10, TPO, EPO, MMP-2, EGFR, MMP-3, ErbB2, cytokeratin-19, E-cadherin, IL-6, osteopontin, cKit, uPA, NSE, cMET, MDC, sFlt-1, CEA, cytokeratin-8, KGF, S100A6, and IL2-R, and combinations thereof;   (b) comparing said level of said plurality of biomarkers and a normal control level of said plurality of biomarkers; and   (c) evaluating from said comparing step (b) that the patient will be responsive to said treatment regimen.   
     
     
         55 . The non-transitory computer readable medium according to  claim 54  wherein said kit comprises at least one of a multi-well assay plate and an assay cartridge. 
     
     
         56 . The non-transitory computer readable medium according to  claim 54  wherein said program performs a method to determine said responsiveness of said lung cancer to said treatment regimen. 
     
     
         57 . The non-transitory computer readable medium according to  claim 55  wherein said multi-well assay plate includes a plurality of assay wells used in an assay conducted in said kit, said plurality of assay wells configured to measure said level of said plurality of biomarkers in said sample. 
     
     
         58 . The non-transitory computer readable medium according to  claim 57  wherein a well of said assay plate comprises a plurality of assay domains, wherein at least two of said assay domains comprises reagents for measuring different biomarkers. 
     
     
         59 . The non-transitory computer readable medium according to  claim 56  wherein said kit comprises said assay cartridge for conducting a plurality of assays, wherein said cartridge comprises a flow cell having an inlet, an outlet, and a detection chamber, wherein said inlet, and said outlet define a flow path through said flow cell, wherein said detection chamber is configured to measure said level of said plurality of biomarkers in said sample. 
     
     
         60 . The non-transitory computer readable medium according to  claim 59  wherein said kit further comprises one or more additional assay reagents used in said assay, said one or more additional assay reagents provided in one or more vials, containers, or compartments of said kit. 
     
     
         61 . The non-transitory computer readable medium according to  claim 57  wherein each of said wells comprises at least four discrete binding domains to which capture antibodies to human analytes are bound, wherein said human analyte is selected from the group consisting of: MDC, NME-2, KGF, P1GF, Flt-3L, HGF, MCP1, SAT-1, MIP-1-b, GCLM, OPG, TNF RH, VEGF-D, ITAC, MMP-10, GPI, PPP2R4, AKR1B1, Amy1A, MIP-1b, P-Cadherin, IP-10, TPO, EPO, MMP-2, EGFR, MMP-3, ErbB2, cytokeratin-19, E-cadherin, IL-6, osteopontin, cKit, uPA, NSE, cMET, MDC, sFlt-1, CEA, cytokeratin-8, KGF, S100A6, and IL2-R. 
     
     
         62 . The non-transitory computer readable medium according to  claim 61  further comprising in one or more vials, containers, or compartments a set of labeled detection antibodies specific for said human analytes and a set of calibrator proteins, wherein said capture antibodies and detection antibodies have been subjected to an analytical testing method selected from the group consisting of Capillary Isoelectric Focusing (CLEF), Size Exclusion Chromatography-Multi-Angle Light Scattering (SEC-MALS), Dynamic Light Scattering (DLS), denaturing/non-denaturing gels, and EXPERION™ automated electrophoresis. 
     
     
         63 . The non-transitory computer readable medium according to  claim 60  wherein said kit further comprises one or more diluents. 
     
     
         64 . The non-transitory computer readable medium according to  claim 62  wherein said detection antibodies are labeled with an electrochemiluminescent (ECL) label. 
     
     
         65 . The non-transitory computer readable medium according to  claim 61  wherein said kit further comprises an ECL read buffer. 
     
     
         66 . The non-transitory computer readable medium according to  claim 61  wherein said discrete binding domains are positioned on an electrode within said well. 
     
     
         67 . The non-transitory computer readable medium according to  claim 62  wherein said set of calibrator proteins comprise a lyophilized blend of proteins. 
     
     
         68 . The non-transitory computer readable medium according to  claim 67  wherein said set of calibrator proteins comprise a liquid formulation of calibrator proteins. 
     
     
         69 . The non-transitory computer readable medium according to  claim 54  wherein a treatment regimen is administered based on said evaluating step (c). 
     
     
         70 . The non-transitory computer readable medium according to  claim 54  wherein said treatment regimen is selected from the group consisting of:
 (i) increasing or decreasing a dosage, frequency, or route of administration of a therapeutic agent of the treatment regimen; 
 (ii) adding an additional therapeutic agent and/or palliative agent to the treatment regimen; and 
 (iii) if the therapeutic regimen comprises the administration of two or more therapeutic and/or palliative agents, modifying the treatment regimen to eliminate one or more of the therapeutic and/or palliative agents. 
 
     
     
         71 . A method for evaluating the efficacy of a first treatment regimen in a patient diagnosed with small cell lung cancer (SCLC) and undergoing the treatment regimen, said method comprising:
 (a) administering a first treatment regimen to said patient wherein said first treatment regimen is administration of one or more of cisplatin, carboplatin irinotecan, etoposide, and vinblastine;   (b) receiving a comparison of a normal control level of biomarkers versus a level of at least two biomarkers in a test sample obtained from said patient undergoing said first treatment regimen for small cell lung cancer, wherein said biomarkers comprise Flt-3L, EGFR, MMP-3, and NME-2 wherein a Receiver Operating Characteristic (ROC) area of each of the markers is at least 0.70;   (c) evaluating from said comparison that said patient is responsive to said first treatment regimen;   (d) identifying the patient as being responsive to said first treatment regimen or not responsive to said first treatment regimen, and performing one of step (e) or step (f), and performing one of:   (e) administering a second treatment regimen if the patient is not responsive to said first treatment regimen, wherein said second treatment regimen is different from the first treatment regimen, and is administration of one or more of cisplatin, irinotecan, etoposide, and vinblastine, or   (f) continuing administration of said first treatment regimen if the patient is responsive to said first treatment regimen.   
     
     
         72 . The method of  claim 71  wherein said comparison comprises receiving results of a multiplexed assay of a plurality of said biomarkers in said test sample, wherein said multiplexed assay is conducted using one reaction volume comprising said test sample. 
     
     
         73 . The method of  claim 72  wherein said assay is conducted in an assay chamber wherein the assay chamber is a well of an assay plate. 
     
     
         74 . The method of  claim 72  wherein said assay chamber is a cartridge. 
     
     
         75 . The method of  claim 71  wherein said test sample is selected from the group consisting of blood, peripheral blood mononuclear cells (PBMC), isolated blood cells, urine, serum, and plasma. 
     
     
         76 . The method of  claim 71  wherein said test sample is serum or plasma. 
     
     
         77 . The method of  claim 71  wherein said test sample is serum. 
     
     
         78 . The method of  claim 71  wherein said sample is plasma. 
     
     
         79 . The method of  claim 71  wherein said levels are compared using an immunoassay. 
     
     
         80 . The method of  claim 71  wherein the comparison is conducted with one or more vials, containers, or compartments, containing a set of calibrator proteins. 
     
     
         81 . The method of  claim 71  wherein the comparison comprises at least four discrete binding domains, which are in the form of a spot pattern. 
     
     
         82 . The method of  claim 71  further comprising at least one of:
 (i) increasing or decreasing a dosage, frequency, or route of administration of a therapeutic agent of the treatment regimen; 
 (ii) adding an additional therapeutic agent and/or palliative agent to the treatment regimen; 
 (iii) if the therapeutic regimen comprises the administration of two or more therapeutic and/or palliative agents, modifying the treatment regimen to eliminate one or more of the therapeutic and/or palliative agents. 
 
     
     
         83 . The method of  claim 71  further comprising measuring a level of a biomarker selected from the group consisting of MDC, NME-2, KGF, P1GF, Flt-3L, HGF, MCP1, SAT-1, MIP-1-b, GCLM, OPG, TNF RH, VEGF-D, ITAC, MMP-10, GPI, PPP2R4, AKR1B1, Amy1A, MIP-1b, P-Cadherin, IP-10, TPO, EPO, EGFR, ErbB2, cytokeratin-19, E-cadherin, IL-6, osteopontin, cKit, uPA, NSE, cMET, MDC, sFlt-1, CEA, cytokeratin-8, KGF, S100A6, and IL2-R.