Methods and compositions of molecular profiling for disease diagnostics

Abstract

The present invention relates to compositions, kits, and methods for molecular profiling and cancer diagnostics, including but not limited to gene expression product markers, alternative exon usage markers, and DNA polymorphisms associated with cancer. In particular, the present invention provides molecular profiles associated with thyroid cancer, methods of determining molecular profiles, and methods of analyzing results to provide a diagnosis.

1 - 78 . (canceled) 
     
     
         79 . A method of detecting whether thyroid cancer cells are present in a test tissue or cell sample from a subject, the method comprising:
 measuring levels of RNA expression of DPP4, SERPINA1, MATN2, and PROS1 in the test tissue or cell sample by microarray analysis and/or quantitative polymerase chain reaction; and   detecting thyroid cancer cells in the test tissue or cell sample by detecting at least a 50% increase in the measured levels of DPP4, SERPINA1, and PROS1 RNA expression and at least a 50% decrease in the measured level of MATN2 RNA expression compared to RNA expression levels of DPP4, SERPINA1, MATN2, and PROS1 in a benign thyroid standard sample.   
     
     
         80 . The method of  claim 79 , further comprising performing fine needle aspiration to obtain the test tissue or cell sample. 
     
     
         81 . The method of  claim 79 , wherein the test tissue sample or cell sample is an unclassified tumor sample. 
     
     
         82 . The method of  claim 79 , further comprising treating the subject. 
     
     
         83 . The method of  claim 79 , wherein the test tissue or cell sample is a formalin fixed test tissue or cell sample. 
     
     
         84 . The method of  claim 79 , wherein the method detects thyroid cancer cells in the test tissue or cell sample with greater than 80% specificity. 
     
     
         85 . The method of  claim 79 , wherein thyroid cancer cells are detected in the test tissue or cell sample when the RNA expression of DPP4, SERPINA1, MATN2, and PROS1 is at least 2.4 fold different as compared to the RNA expression DPP4, SERPINA1, MATN2, and PROS1 in the benign thyroid standard sample. 
     
     
         86 . A method of detecting thyroid cancer cells in a test tissue sample, the method comprising:
 obtaining the test thyroid tissue sample from a subject by fine needle aspirate;   measuring the levels of RNA expression of DPP4, SERPINA1, MATN2, and PROS1 in the test thyroid tissue sample by microarray analysis; and   detecting thyroid cancer cells in the test tissue or cell sample by detecting at least a 50% increase in the measured levels of DPP4, SERPINA1, and PROS1 RNA expression and at least a 50% decrease in the measured level of MATN2 RNA expression compared to the RNA expression levels of DPP4, SERPINA1, MATN2, and PROS1 in a benign thyroid standard sample.   
     
     
         87 . The method of  claim 86 , wherein thyroid cancer cells are detected in the test thyroid tissue sample when the RNA expression of DPP4, SERPINA1, MATN2, and PROS1 is at least 2.4 fold different as compared to the RNA expression DPP4, SERPINA1, MATN2, and PROS1 in the benign thyroid standard sample. 
     
     
         88 . The method of  claim 86 , further comprising treating the subject. 
     
     
         89 . The method of  claim 86 , wherein the test tissue sample is an unclassified tumor sample.