Methods for prognosis and treatment of solid tumors

• US 20060194211A1
• Filed: 04/29/2004
• Published: 08/31/2006
• Est. Priority Date: 04/29/2003
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Twine, Natalie C., Dorner, Andrew J., Trepicchio, William L., Burczynski, Michael E., Immermann, Fred, Slonim, Donna K., Strahs, Andrew
• Application Number:
  US10/834,268
• Publication Number:
  US 20060194211A1
• Time in Patent Office: Days
• US Class Current: 435/6.14
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57438 of liver, pancreas or kidney
• CPC Class Codes: G01N 33/57496 involving intracellular compounds
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 Gene or protein expression profiling; Expression-ratio estimation or normalisation

Abstract

Solid tumor prognosis genes, and methods, systems and equipment of using these genes for the prognosis and treatment of solid tumors. Prognosis genes for a solid tumor can be identified by the present invention. The expression profiles of these genes in peripheral blood mononuclear cells (PBMCs) are correlated with clinical outcome of the solid tumor. The prognosis genes of the present invention can be used as surrogate markers for predicting clinical outcome of a solid tumor in a patient of interest. These genes can also be used to select a treatment which has a favorable prognosis for the solid tumor of the patient of interest.

Claims

1. A method comprising comparing an expression profile of at least one gene in a peripheral blood sample of a patient to at least one reference expression profile of said at least one gene, wherein the patient has a solid tumor, and each of said at least one gene is differentially expressed in peripheral blood mononuclear cells of a first class of patients as compared to peripheral blood mononuclear cells of a second class of patients, wherein both the first and second classes of patients have the solid tumor, and wherein the first class of patients has a first clinical outcome, and the second class of patients has a second clinical outcome.

2. The method according to claim 1, wherein the first and second clinical outcomes are outcomes of a therapeutic treatment of the solid tumor in the first and second classes of patients.

3. The method according to claim 2, wherein the expression profile and said at least one reference expression profile are baseline expression profiles for the therapeutic treatment.

4. The method according to claim 2, wherein the peripheral blood sample is a whole blood sample.

5. The method according to claim 2, wherein the peripheral blood sample comprises enriched peripheral blood mononuclear cells.

6. The method according to claim 2, wherein the solid tumor is RCC, and the therapeutic treatment comprises a CCI-779 therapy.

7. The method according to claim 6, wherein the first clinical outcome is TTD of less than a first specified period of time starting from initiation of the therapeutic treatment, and the second clinical outcome is TTD of longer than a second specified period of time starting from initiation of the therapeutic treatment.

8. The method according to claim 6, wherein the first clinical outcome is TTP of less than a specified period of time starting from initiation of the therapeutic treatment, and the second clinical outcome is TTP of longer than another specified period of time starting from initiation of the therapeutic treatment.

9. The method according to claim 6, wherein the first clinical outcome is a Motzer risk classification, and the second clinical outcome is another Motzer risk classification.

10. The method according to claim 2, wherein said at least one gene comprises two or more genes, and said at least one reference expression profile includes a first reference expression profile and a second reference expression profile, wherein the first reference expression profile is an average expression profile of said at least one gene in peripheral blood samples of patients selected from the first class, and the second reference expression profile is an average expression profile of said at least one gene in peripheral blood samples of patients selected from the second class, and wherein the expression profile is compared to said at least one reference expression profile by using a k-nearest-neighbors or weighted voting algorithm.

11. The method according to claim 1, wherein said at least one gene substantially correlates with a class distinction between the first class and the second class.

12. The method according to claim 1, comprising selecting a therapy for treating the solid tumor in the patient, wherein the patient has a favorable prognosis for the therapy.

13. A method comprising comparing an expression profile of at least one gene in a peripheral blood sample of a patient to at least one reference expression profile of said at least one gene, wherein the patient has a solid tumor, and each of said at least one gene is differentially expressed in peripheral blood mononuclear cells of a first class of patients as compared to peripheral blood mononuclear cells of a second class of patients, wherein the first and second classes of patients have the solid tumor, and each of the first and second classes is a subcluster formed by an unsupervised clustering analysis of gene expression profiles in peripheral blood mononuclear cells of a population of patients who have the solid tumor, and wherein the majority of the first class of patients has a first clinical outcome, and the majority of the second class of patients has a second clinical outcome.

14. The method according to claim 13, wherein the first and second clinical outcomes are outcomes of a therapeutic treatment of the solid tumor in the first and second classes of patients, and the expression profile and said at least one reference expression profile are baseline expression profiles for the therapeutic treatment.

15. The method according to claim 14, wherein the solid tumor is RCC, and the therapeutic treatment comprises a CCI-779 therapy.

16. The method according to claim 13, comprising selecting a therapy for treating the solid tumor in the patient, wherein the patient has a favorable prognosis for the therapy.

17. A method comprising comparing an expression profile of at least one gene in a peripheral blood sample of a patient to at least one reference expression profile of said at least one gene, wherein the patient has a solid tumor, and expression levels of each of said at least one gene in peripheral blood mononuclear cells of patients who have the solid tumor correlate with clinical outcomes of said patients.

18. The method according to claim 17, wherein the solid tumor is RCC, and said clinical outcomes are measured by patient response to a CCI-779 therapy, and wherein said at least one gene comprises one or more genes selected from Tables 6a, 6b, 6c, 6d, 9a, 9b, 9c, 9d, 10, 11, 12, 13, 16, 20, and 21.

19. A system comprising:

a memory or a storage medium including data that represent an expression profile of at least one gene in a peripheral blood sample of a patient who has a solid tumor;

at least another storage medium including data that represent at least one reference expression profile of said at least one gene;

a program capable of comparing the expression profile to said at least one reference expression profile; and

a processor capable of executing the program, wherein expression levels of said at least one gene in peripheral blood mononuclear cells of patients who have the solid tumor correlate with clinical outcomes of said patients.

20. A nucleic acid or protein array comprising concentrated probes for solid tumor prognosis genes, wherein each of the solid tumor prognosis genes is differentially expressed in peripheral blood mononuclear cells of a first class of patients as compared to peripheral blood mononuclear cells of a second class of patients, wherein both the first and second classes of patients have a solid tumor, and wherein the first class of patients has a first clinical outcome, and the second class of patients has a second clinical outcome.