Gene expression profiles in liver cancer

• US 6,974,667 B2
• Filed: 06/14/2001
• Issued: 12/13/2005
• Est. Priority Date: 06/14/2000
• Status: Expired due to Fees

• Current Assignee: Gene Logic, Inc. (Steel Partners Holdings LP)
• Original Assignee: Gene Logic, Inc. (Steel Partners Holdings LP)
• Inventors: Vockley, Joseph, Horne, Darci T., Scherf, Uwe
• Primary Examiner(s): SITTON, JEHANNE SOUAYA
• Application Number:
  US09/880,107
• Publication Number:
  US 20020142981A1
• Time in Patent Office: 1,643 Days
• Field of Search: 435/6, 435/91.1, 435/91.2, 536/23.1, 536/24.3, 536/22.1, 935/6, 436/518
• US Class Current: 435/6.14
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• 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
• 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
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The present invention identifies the global changes in gene expression associated with liver cancer by examining gene expression in tissue from normal liver, metastatic malignant liver and hepatocellular carcinoma. The present invention also identifies expression profiles which serve as useful diagnostic markers as well as markers that can be used to monitor disease states, disease progression, drug toxicity, drug efficacy and drug metabolism.

Claims

1. A method of diagnosing hepatocellular carcinoma in a human patient, compnsing:

(a) detecting the level of expression in a tissue sample of ten or more genes from Tables 3A, 3B, 5, 7A, 7B, 8A, and 8B;

wherein differential expression of the genes in Tables 3A, 3B, 5, 7A, 7B, 8A, and 8B is indicative of hepatocellular carcinoma.

8. A method of claim 1 or 4, wherein the level of expression of 100 or more genes from one or more tables selected from the group consisting of Tables 3A, 3B, 4A, 4B, 5, 6A, 6B, 7A, 7B, 8A, 8B, 9A and 9B is detected.

9. A method of claim 1 or 4, wherein the level of expression is compared to the gene information in one or more tables selected from the group consisting of Tables 3A, 3B, 4A, 4B, 5, 6A, 6B, 7A, 7B, 8A, 8B, 9A and 9B.

2. A method of detecting the progression of hepatocellular carcinoma in a human patient, comprising:

(a) detecting the level of expression in a tissue sample of ten or more genes from Tables 3A, 3B, 5, 7A, 7B, 8A, and 8B;

wherein differential expression of the genes in Tables 3A, 3B, 5, 7A, 7B, 8A, and 8B is indicative of hepatocellular carcinoma progression.

3. A method of monitoring the treatment of a human patient with hepatocellular carcinoma, comprising:

(a) administering a pharmaceutical composition to the patient;

(b) detecting the level of expression of ten or more genes from Tables 3A, 3B, 5, 7A, 7B 8A and 8B from a cell or tissue sample from the patient; and

(c) comparing the patient gene expression detected in step (b) to gene expression from a cell population comprising normal liver cells or to gene expression from a cell population comprising hepatocellular carcinoma cells or both.

4. A method of diagnosing a metastatic liver cancer in a human patient, comprising:

(a) detecting the level of expression in a tissue sample of ten or more genes from Tables 4A, 4B, 5, 6A, 6B, 9A and 9B;

wherein differential expression of the genes in Tables 4A, 4B, 5, 6A, 6B, 9A, and 9B is indicative of metastatic liver cancer.

5. A method of detecting the progression of a metastatic liver cancer in a human patient, comprising:

(a) detecting the level of expression in a tissue sample of ten or more genes from Tables 4A, 4B, 5, 6A, 6B, 9A and 9B;

wherein differential expression of the genes in Tables 4A, 4B, 5, 6A, 6B, 9A, and 9B is indicative of metastatic liver cancer progression.

6. A method of monitoring the treatment of a human patient with metastatic liver cancer, comprising:

(a) administering a pharmaceutical composition to the patient;

(b) detecting the level of expression of ten or more genes from Tables 4A, 4B, 5, 6A, 6B, 9A and 9B from a cell or tissue sample from the patient; and

(c) comparing the patient gene expression detected in step (b) to gene expression from a cell population comprising normal liver cells or to gene expression from a cell population comprising metastatic liver tumor cells or both.

7. A method of differentiating metastatic liver cancer from hepatocellular carcinoma in a human patient, comprising:

(a) detecting the level of expression in a tissue sample of ten or more genes from Tables 3-9;

wherein differential expression of the genes in Tables 3-9 is indicative of metastatic liver cancer rather than hepatocellular carcinoma.

10. A method of diagnosing hepatocellular carcinoma or metastatic liver cancer in a human patient comprising:

(a) detecting the level of expression of ten or more genes from Tables 3-9 from a tissue sample from the patient; and

(b) comparing the gene expression detected in step (a) to a database comprising part of the data in Tables 3-9;

wherein differential expression of the genes detected in step (a) is indicative of hepatocellular carcinoma or metastatic liver cancer.

11. A method of claim 10, wherein the cancer is hepatocellular carcinoma.

12. A method of claim 10, wherein the cancer is metastatic liver cancer.

13. A method of claim 10, wherein the database comprises all of the data from Tables 3-9.

14. A method of claim 10, wherein the database comprises gene expression information for all of the genes from Tables 3-9.

15. A method of diagnosing hepatocellular carcinoma in a human patient, comprising:

(a) detecting the level of expression in a liver tissue sample of ten or more mRNA species from Table 3A, 3B, 5, 7A, 7B, 8A or 8B; and

(b) comparing the detected level of expression to the level of expression of said ten or more mRNA species in a hepatocellular carcinoma liver tissue sample, thereby diagnosing hepatocellular carcinoma in the patient.

17. A method of claim 15, wherein the level of expression of said ten or more mRNA species in a hepatocellular carcinoma liver sample is in Table 3A, 3B, 5, 7A, 7B, 8A or 8B.

16. A method of diagnosing metastatic liver cancer in a human patient, comprising:

(a) detecting the level of expression in a liver tissue sample of ten or more mRNA species from Table 4A, 4B, 5, 6A, 6B, 9A or 9B; and

(b) comparing the detected level of expression to the level of expression of said ten or more mRNA species in a metastatic liver cancer tissue sample, thereby diagnosing metastatic liver cancer in the patient.

18. A method of claim 16, wherein the level of expression of said ten or more mRNA species in a metastatic liver cancer sample is in Table 4A, 4B, 5, 6A, 6B, 9A or 9B.