Diagnostic tests using gene expression ratios
The invention provides methods for diagnosing biological states or conditions based on ratios of gene expression data from cell or tissue samples, such as cancer cell or tissue samples. The invention also provides sets of genes that are expressed differentially in normal and cancer lung cells and tissues. These sets of genes can be used to discriminate between normal and malignant cells or tissues, and between classes of malignant cells or 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 identifying a lung cell or tissue in a sample comprising
measuring the expression levels of a set of genes in a lung tumor tissue sample, wherein the set of genes comprises (i) at least one upregulated gene that is overexpressed in lung adenocarcinoma compared to lung squamous cell carcinoma, the at least one upregulated gene being selected from the genes listed in Table 6, and (ii) at least one downregulated gene that is less expressed in lung adenocarcinoma compared to lung squamous cell carcinoma, the at least one downregulated gene being selected from the genes listed in Table 7.
2. The method of claim 1 , wherein the expression levels of the set of genes are measured by nucleic acid hybridization, nucleic acid amplification, or an immunological method.
3. The method of claim 1 , wherein the measuring and calculating steps are performed by a diagnostic system.
4. The method of claim 2 , wherein the upregulated and downregulated genes are selected as having statistically significant differences in mean expression levels.
5. The method of claim 2 , wherein there is at least a 2-fold difference in mean expression levels between the at least one upregulated gene (A) and the at least one downregulated gene (B).
6. The method of claim 2 , wherein two or more expression ratios (R 1 , R 2 , . . . , R n ) are calculated.
7. The method of claim 6 , further comprising combining the two or more expression ratios (R 1 , R 2 , . . . , R n ).
8. The method of claim 7 , wherein the step of combining the two or more expression ratios comprises calculating the geometric mean of the two or more expression ratios using the following formula: (R 1 R 2 . . . R n ) 1/n , wherein R represents a single ratio value.
9. The method of claim 2 , wherein the ratio is calculated by division of the expression level of one upregulated gene by the expression level of one downregulated gene using the formula A/B.
10. The method of claim 2 , wherein the ratio is calculated by division of the expression levels of two or more upregulated genes (A 1 , A 2 , . . . , A n ) by the expression level of one downregulated gene (B) using the formula ((A 1 A 2 . . . A n ) 1/n /B).
11. The method of claim 2 , wherein the ratio is calculated by division of the expression level of one upregulated gene (A) by the expression levels of two or more downregulated genes (B 1 , B 2 , . . . , B m ) using the formula (A/(B 1 B 2 . . . B m ) 1/m ).
12. The method of claim 2 , wherein the ratio is calculated by division of the expression levels of two or more upregulated genes (A 1 , A 2 , . . . , A n ) by the expression levels of two or more downregulated genes (B 1 , B 2 , . . . , B m ) using the formula (A 1 A 2 . . . A n ) 1/n /(B 1 B 2 . . . B m ) 1/m .
13. The method of claim 3 , further comprising transforming the expression level data for the upregulated and/or downregulated genes prior to calculating the ratio.
14. The method of claim 13 , wherein the transforming step is performed by a transformation device included in the diagnostic system.
15. The method of claim 1 , further comprising identifying a treatment based on presence of the type of the lung cancer cell or tissue in the sample.