Lung cancer markers and uses thereof

Abstract

Methods and compositions are provided for assessing (e.g., diagnosing), treating, and preventing diseases, especially cancer, and particular lung cancer, using lung cancer markers (LCM). Individual LCM and panels comprising multiple LCM are provided for these and other uses. Methods and compositions are also provided for determining or predicting the effectiveness of a treatment or for selecting a treatment using LCM. Methods and compositions are further provided for modulating cell function using LCM. Also provided are compositions that modulate LCM (e.g., antagonists or agonists), such as antibodies, proteins, small molecule compounds, and nucleic acid agents (e.g., RNAi and antisense agents), as well as pharmaceutical compositions thereof. Further provided are methods of screening for agents that modulate LCM, and agents identified by these screening methods.

1 . A method of detecting lung cancer in an individual, the method comprising detecting the level of TFPI in a sample from said individual, wherein an elevated level of TFPI indicates that said individual has lung cancer. 
     
     
         2 . The method of  claim 1 , further comprising detecting the level of at least one marker selected from the group consisting of Cyfra, SLPI, TIMP1, SCC, CEACAM5, MMP2, OPN, and MDK in a sample from said individual, wherein an elevated level of the marker indicates that said individual has lung cancer. 
     
     
         3 . The method of  claim 2 , wherein the method comprises detecting the levels of the markers Cyfra, SLPI, TIMP1, CEACAM5, and MDK, wherein elevated levels of a plurality of said markers indicate that said individual has lung cancer. 
     
     
         4 . The method of  claim 3 , wherein the method further comprises detecting the levels of the markers SCC, MMP2, and OPN, wherein elevated levels of a plurality of said markers indicate that said individual has lung cancer. 
     
     
         5 . A method of detecting lung cancer in an individual, the method comprising detecting the levels of a panel of markers selected from the group consisting of the panels provided in Table 5, wherein elevated levels of a plurality of said markers indicate that said individual has lung cancer. 
     
     
         6 - 17 . (canceled) 
     
     
         18 . The method of  claim 4 , wherein the detecting comprises detecting the marker by immunoassay. 
     
     
         19 . The method of  claim 18 , wherein the immunoassay is ELISA. 
     
     
         20 - 21 . (canceled) 
     
     
         22 . The method of  claim 2 , wherein the detecting comprises contacting the sample with an antibody that selectively binds to the marker and detecting the binding of the antibody to the marker. 
     
     
         23 - 27 . (canceled) 
     
     
         28 . A kit comprising at least one container and detection reagents for detecting a plurality of lung cancer markers comprising Cyfra, SLPI, TIMP1, SCC, TFPI, CEACAM5, MMP2, OPN, and MDK, wherein the detection reagents are stored in one or more of the containers. 
     
     
         29 . The kit of  claim 28 , wherein the detection reagents are antibodies or antigens for use in an immunoassay. 
     
     
         30 . The kit of  claim 28 , wherein at least one of the detection reagents is labeled with a detectable moiety. 
     
     
         31 . The kit of  claim 29 , wherein the immunoassay is an ELISA. 
     
     
         32 . The kit of  claim 28 , wherein the detection reagents are antibodies, and wherein the antibodies are at least one of monoclonal, polyclonal, fully human, humanized, chimeric, single-chain, and anti-idiotypic antibodies. 
     
     
         33 . The kit of  claim 28 , wherein the detection reagents are antibodies, and wherein the antibodies comprise an antibody fragment selected from the group consisting of:
 a) an Fab fragment;   b) an F(ab′) 2  fragment; and   c) an Fv fragment.   
     
     
         34 . The method of  claim 4 , wherein the sample is a serum sample. 
     
     
         35 . The method of  claim 4 , further comprising the step of providing a prognosis to the individual. 
     
     
         36 . The method of  claim 4 , wherein the method is carried out following lung cancer treatment. 
     
     
         37 . The method of  claim 4 , further comprising selecting a lung cancer treatment for administration to an individual based on the level of a plurality of said markers, and administering the treatment to the individual. 
     
     
         38 . The method of  claim 4 , further comprising selecting said individual for inclusion in a clinical trial of a therapeutic agent. 
     
     
         39 - 43 . (canceled) 
     
     
         44 . The method of claim  17 , wherein the method is carried out in conjunction with lung cancer treatment. 
     
     
         45 . The method of  claim 44 , wherein the earlier time point is before the lung cancer treatment and the later time point is after the lung cancer treatment. 
     
     
         46 . The method of  claim 44 , wherein the lung cancer treatment comprises at least one of administration of a therapeutic agent, surgical resection of at least a portion of a lung tumor, or radiation therapy. 
     
     
         47 - 50 . (canceled) 
     
     
         51 . The method of  claim 5 , wherein said elevated levels are either greater than predetermined cutoff levels, or greater than or equal to predetermined cutoff levels. 
     
     
         52 . (canceled) 
     
     
         53 . The method of  claim 5 , wherein said panel is selected from the group consisting of the following panels:
 panels comprising the 9-marker panel (Cyfra, SLPI, TIMP1, SCC, TFPI, CEACAM5, MMP2, OPN, and MDK); and   panels comprising the 6-marker subset of the 9-marker panel (Cyfra, SLPI, TIMP1, TFPI, CEACAM5, and MDK).   
     
     
         54 . The method of  claim 53 , wherein the panel further comprises at least one marker selected from the group consisting of the markers provided in Table 4. 
     
     
         55 . The method of  claim 2 , wherein the method comprises detecting the levels of the markers TFPI, Cyfra, SCC, and CEACAM5. 
     
     
         56 . The method of  claim 55 , further comprising detecting the levels of at least one marker selected from the group consisting of TIMP1 and OPN. 
     
     
         57 . The method of  claim 56 , further comprising detecting the level of MDK.