Diagnostic and Prognostic Tests

Abstract

The invention provides methods for diagnosing biological states or conditions based on ratios of gene expression data from tissue samples, such as cancer tissue samples. The invention also provides sets of genes that are expressed differentially in malignant pleural mesothelioma. These sets of genes can be used to discriminate between normal and malignant tissues, and between classes of malignant tissues. Accordingly, diagnostic assays for classification of tumors, prediction of tumor outcome, selecting and monitoring treatment regimens and monitoring tumor progression/regression also are provided.

1 . A method for diagnosing the presence of cancer cells or non-cancer cells in a tissue sample, comprising
 providing a set of two or more genes, wherein the set comprises at least one upregulated gene that is expressed in greater amounts in the cancer cells than in corresponding non-cancer cells and at least one downregulated gene that is expressed in lesser amounts in cancer cells than in corresponding non-cancer cells,   determining the expression levels of the set of two or more genes,   calculating at least one ratio of the expression level of the at least one upregulated gene to the expression level of the at least one downregulated gene, wherein the at least one ratio is indicative of the presence of cancer cells or non-cancer cells in the tissue sample.   
     
     
         2 . The method of  claim 1 , wherein there is at least a 2-fold difference in mean expression levels between the at least one upregulated gene and the at least one downregulated gene. 
     
     
         3 . The method of  claim 1 , wherein two or more expression ratios are calculated. 
     
     
         4 . The method of  claim 3 , further comprising combining the two or more expression ratios. 
     
     
         5 . The method of  claim 4 , wherein the step of combining the two or more expression ratios comprises calculating the geometric mean of the two or more expression ratios. 
     
     
         6 . The method of  claim 1 , wherein the ratio is calculated by division of the expression level of one upregulated gene by the expression level of one downregulated gene. 
     
     
         7 . The method of  claim 1 , wherein the ratio is calculated by division of the expression levels of two or more upregulated genes by the expression level of one downregulated gene. 
     
     
         8 . The method of  claim 1 , wherein the ratio is calculated by division of the expression level of one upregulated gene by the expression levels of two or more downregulated genes. 
     
     
         9 . The method of  claim 1 , wherein the ratio is calculated by division of the expression levels of two or more upregulated genes by the expression levels of two or more downregulated genes. 
     
     
         10 . The method of  claim 1 , further comprising transforming the expression level data for the upregulated and/or downregulated genes prior to calculating the ratio. 
     
     
         11 . The method of  claim 1 , wherein the expression levels are determined by a method selected from the group consisting of nucleic acid hybridization and nucleic acid amplification. 
     
     
         12 . The method of  claim 11 , wherein the nucleic acid hybridization is performed using a solid-phase nucleic acid molecule array. 
     
     
         13 . The method of  claim 11 , wherein the nucleic acid amplification method is real-time PCR. 
     
     
         14 . The method of  claim 1 , wherein the expression levels are determined by an immunological method. 
     
     
         15 . The method of  claim 14 , wherein the immunological method is performed using a solid-phase antibody array. 
     
     
         16 . The method of  claim 14 , wherein the immunological method is an ELISA or ELISPOT assay. 
     
     
         17 . The method of  claim 1 , wherein the cancer is selected from the group consisting of malignant pleural mesothelioma, lung adenocarcinoma, squamous carcinoma, medulloblastoma, prostate cancer, breast cancer, diffuse large B-cell lymphoma, follicular lymphoma and ovarian cancer. 
     
     
         18 . The method of  claim 1 , wherein the at least one ratio is indicative of the presence of cancer cells in the tissue sample. 
     
     
         19 . The method of  claim 1 , wherein the at least one ratio is indicative of the presence of non-cancer cells in the tissue sample.