Biomarkers of Rapid Progression in Advanced Non-Small Cell Lung Cancer

Abstract

Methods and kits for identifying rapidly progressing lung cancer in a subject are provided. The method includes obtaining a biological sample from the subject and assaying a level of a biomarker in a biomarker panel in the biological sample where the panel includes at least one biomarker selected from Table I or Table II. The method further includes determining with the subject is treatment naïve or has received at least one treatment; and comparing the level of the biomarker in the subject's sample to a cutoff value listed in Table I for treatment naïve subjects or Table II for previously treated subjects. The method further includes determining whether the subject's level is above or below the cutoff value to determine whether the subject has rapidly progressing lung cancer.

1 . A method for identifying rapidly progressing lung cancer in a subject, the method comprising:
 obtaining a biological sample from the subject;   assaying a level of a biomarker in a biomarker panel in the biological sample, the panel comprising at least one biomarker selected from Table I or Table II;   determining whether the subject is treatment naïve or has received at least one treatment;   comparing the level of the biomarker in the subject's sample to a cutoff value listed in Table I for treatment naïve subjects or Table II for previously treated subjects;   determining whether the subject's level is above or below the cutoff value to determine whether the subject has rapidly progressing lung cancer.   
     
     
         2 . The method according to  claim 1 , wherein the at least one biomarker assayed has a p-value p≤0.05. 
     
     
         3 . The method according to  claim 1 , wherein the at least one biomarker assayed has a p-value where p≤0.01. 
     
     
         4 . The method according to  claim 1 , comprising determining the level of at least two biomarkers selected from Table I for treatment naïve subjects or from Table II for previously treated subjects. 
     
     
         5 . The method according to  claim 1 , comprising determining the level of the biomarker for the panel of biomarkers wherein the at least one biomarker in the panel is selected from sTNFRI, sTNFRII, CA 19-9, Follistatin, Total PSA, TNF-α and IL-6 for treatment naïve subjects. 
     
     
         6 . The method according to  claim 1 , comprising determining the level of the biomarker for the panel of biomarkers wherein the at least one biomarker in the panel comprises TRAIL, sTNFRI, IGFBP-1, sEGFR, IGF-1, TGF-β, HGF, MMP-7, MMP-2, α-fetoprotein, Osteopontin, sVEGFR2 and IL-6 for the pretreated subjects. 
     
     
         7 . The method according to  claim 1 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         8 . The method according to  claim 1 , wherein the biological sample comprises plasma sample or serum sample. 
     
     
         9 . The method according to  claim 1 , further comprising modifying a treatment regime for the subject when the comparison indicates that the subject has rapidly progressing lung cancer. 
     
     
         10 . A kit for performing the measurement of the level of the biomarker of the subject in  claim 1 , wherein the kit comprises reagents for measuring the at least one biomarker. 
     
     
         11 . The kit according to  claim 10 , wherein the kit comprises reagents for measuring serum or plasma. 
     
     
         12 . The kit according to  claim 10 , wherein the kit comprises reagents for measuring the at least one biomarker in the panel wherein the at least one biomarker has a p-value where p≤0.05. 
     
     
         13 . The kit according to  claim 10 , wherein the kit comprises reagents for measuring the at least one biomarker in the panel wherein the at least one biomarker is selected from sTNFRI, sTNFRII, CA 19-9, Follistatin, Total PSA, TNF-α and IL-6 for treatment naïve subjects. 
     
     
         14 . The kit according to  claim 10 , wherein the kit comprises reagents for measuring the at least one biomarker, wherein the at least one biomarker is selected from TRAIL, sTNFRI, IGFBP-1, sEGFR, IGF-1, TGF-β, HGF, MMP-7, MMP-2, α-fetoprotein, Osteopontin, sVEGFR2 and IL-6 for the pretreated subjects.