Molecular characteristics of non-small cell lung cancer

• US 7,332,590 B2
• Filed: 08/16/2002
• Issued: 02/19/2008
• Est. Priority Date: 08/16/2001
• Status: Expired due to Fees

• Current Assignee: Johns Hopkins University, Esoterix Genetic Laboratories LLC (Laboratory Corporation Of America Holdings), The United States of America As Represented By The Secretary of Agriculture
• Original Assignee: Johns Hopkins University, Genzyme Corporation (Sanofi ), United States Department Of Health And Human Services
• Inventors: Sidransky, David, Jen, Jin, Dracheva, Tatiana, Nacht, Mariana, Madden, Stephen
• Primary Examiner(s): Horlick; Kenneth R.
• Assistant Examiner(s): Tung; Joyce
• Application Number:
  US10/486,844
• Publication Number:
  US 20050136403A1
• Time in Patent Office: 2,013 Days
• Field of Search: 536/23.1, 435/6, 435/91.2, 424/9.1
• US Class Current: 536/23.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21^WAF1/CIP1 and 14-3-3σ, were consistently under-expressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression observed by SAGE were consistent with the results obtained by quantitative real-time PCR or cDNA array analyses using 43 additional lung tumor and normal samples. Thus, although derived from only a few tissue libraries, molecular signatures of non-small cell lung cancer derived from SAGE most likely represent an unbiased yet distinctive molecular signature for human lung cancer.

Claims

1. A method of associating a lung cancer with squamous cell carcinoma comprising:

determining an amount of a gene product of a gene in a lung cancer sample, said gene selected from the group consisting of;

aldoketoreductase family 1, member B 10 (NM_—

020299), peroxiredoxin 1 (PRDX1;

NM_—

002574), and TNF receptor superfamily member 18 (TNFRSF18;

NM004195);

comparing the amount of the gene product to the amount determined in a lung tissue sample which is non-pathological, wherein an increased amount of the gene product in the lung cancer sample relative to the lung tissue sample which is non-pathological associates the lung cancer with a squamous cell carcinoma.

2. The method of claim 1 further comprising the step of using the determined comparative gene product information to formulate a diagnosis.

3. The method of claim 1 further comprising the step of using the determined comparative gene product information to formulate a prognosis.

4. The method of claim 1 further comprising the step of using the determined comparative gene product information to formulate a treatment plan.

5. The method of claim 1 wherein the gene product of aldoketoreductase is determined.

6. The method of claim 1 wherein the gene product of PRDX1 is determined.

7. The method of claim 1 wherein the gene product of TNF receptor 18 is determined.

8. The method of claim 1 wherein the gene product is mRNA.

9. The method of claim 1 wherein the gene product is protein.

10. The method of claim 1 wherein the lung tissue sample which is non-pathological comprises normal lung small airway epithelial cells.

11. The method of claim 1 wherein the lung tissue sample which is non-pathological comprises normal bronchial/tracheal epithelial cells.

12. The method of claim 1 wherein the amount of the gene product is determined using a microarray.

13. The method of claim 12 wherein cRNA is hybridized to probes on the microarray to determine the amount of the gene product.

14. A method of associating a lung cancer with adenocarcinoma, comprising:

determining an amount of a gene product of a small proline-rich protein 3 (SPRR3;

NM₁₃ 005416) gene in a lung cancer sample;

comparing the amount of the gene product to the amount determined in a lung tissue sample which is non-pathological. wherein a decreased amount of the gene product in the lung cancer sample relative to the lung tissue sample which is non-pathological associates the lung cancer with adenocarcinoma.

15. The method of claim 14 further comprising the step of using the determined comparative gene product information to formulate a diagnosis.

16. The method of claim 14 further comprising the step of using the determined comparative gene product information to formulate a prognosis.

17. The method of claim 14 further comprising the step of using the determined comparative gene product information to formulate a treatment plan.

18. The method of claim 14 wherein the gene product is mRNA.

19. The method of claim 14 wherein the gene product is protein.

20. The method of claim 14 wherein the lung tissue sample which is non-pathological comprises normal lung small airway epithelial cells.

21. The method of claim 14 wherein the lung tissue sample which is non-pathological comprises normal bronchial/tracheal epithelial cells.

22. The method of claim 14 wherein the amount of the gene product is determined using a microarray.

23. The method of claim 22 wherein cRNA is hybridized to probes on the microarray to determine the amount of the gene product.