Methods for detecting hepatocellular carcinoma

• US 8,357,489 B2
• Filed: 11/13/2009
• Issued: 01/22/2013
• Est. Priority Date: 11/13/2008
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc., Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Original Assignee: Agilent Technologies, Inc., Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Inventors: Chua, Mei-Sze, Sun, Hongbo, Yang, Dan-Hui Dorothy, Tsalenko, Anya, Peter, Brian Jon, So, Samuel
• Primary Examiner(s): AEDER, SEAN E
• Application Number:
  US12/618,376
• Publication Number:
  US 20100120631A1
• Time in Patent Office: 1,166 Days
• Field of Search: None
• US Class Current: 435/6.1
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/60 Complex ways of combining multiple protein biomarkers for diagnosis
• CPC Class Codes: G01N 33/57438 of liver, pancreas or kidney
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites

Abstract

A method for evaluating hepatocellular carcinoma in a subject is provided. In certain embodiments, the method comprises: a) obtaining a hepatocellular carcinoma protein marker profile for a sample obtained from the subject; and b) comparing the protein marker profile to a control profile.

Claims

1. A method of distinguishing hepatocellular carcinoma (HCC) from viral induced cirrhosis in a subject, comprising:

a) measuring levels of at least three HCC markers selected from one or both of a first group (i) and a second group (ii) of markers in a biological sample from said subject to obtain a hepatocellular carcinoma marker profile from said subject;

b) comparing said marker profile to a control profile obtained from a viral-induced cirrhosis control sample, wherein differential expression of the at least three HCC markers in said biological sample compared to the control sample indicates a diagnosis of hepatocellular carcinoma in said subject; and

wherein

c) said differential expression comprises decreased expression in said first group of HCC markers and increased expression in said second group of HCC markers, and wherein

d) said first group (i) consists of L-Selectin, IGFBP-6, IL-6sR, VCAM-1, FGF-basic, Fractalkine/CX3CL1, IL18; and

e) said second group (ii) consists of β

-Catenin, M-CSF, IL-8, MMP-10, Total p21, IL-1 ra, Resistin, interferon-gamma, BRAK/CXCL14, TNF-beta.

3. The method according to one of claim 1 or 2, wherein said sample is whole blood, blood serum or blood plasma.

4. The method according to one of claim 1 or 2, wherein said obtaining a hepatocellular carcinoma marker profile comprises:

contacting said sample with capture agents that specifically bind to hepatocellular carcinoma protein markers;

detecting binding of proteins in said sample to said capture agents;

wherein an alteration in said binding, compared to a control sample, is indicative of hepatocellular carcinoma.

5. The method according to one of claim 1 or 2, wherein said sample is contacted with a panel of capture agents that specifically bind to said hepatocellular carcinoma protein markers.

6. The method according to one of claim 1 or 2, furthermore assessing clinical indicia.

7. The method according to claim 6, wherein said clinical indicia comprise symptoms of HCC.

8. The method according to claim 1, wherein said method is combined with an alpha-fetoprotein (AFP) blood test to provide a diagnosis of HCC.

9. A method comprising:

a) receiving a sample;

b) evaluating said sample according to the method of one of claim 1 or 2 to produce an indication of hepatocellular carcinoma (HCC) of a subject; and

c) communicating said results.

10. The method of claim 9, wherein said sample is received from a remote location.

11. The method of claim 9, wherein said sample is communicated to a remote location.

12. The method according to claim 1, wherein comparing hepatocellular carcinoma marker profiles comprises use of a computer readable medium comprising instructions for comparing a hepatocellular carcinoma marker profile to a control profile to provide a diagnosis of HCC.

13. The method according to claim 1, wherein said subject has alpha-fetoprotein serum levels of less than 20 μ

g/l.

14. The method according to one of claim 1 or 2, wherein said method furthermore provides an indication of disease progression.

2. A method of distinguishing hepatocellular carcinoma (HCC) from viral induced cirrhosis in a subject, comprising:

a) measuring levels of at least one HCC marker selected from the group consisting of M-CSF and MMP-10 in a biological sample from said subject to obtain a hepatocellular carcinoma marker profile from said subject;

b) comparing said marker profile to a control profile obtained from a viral-induced cirrhosis control sample, wherein increased expression of the at least one HCC marker in said biological sample compared to the control profile indicates a diagnosis of hepatocellular carcinoma in said subject.

15. The method according to claim 2, wherein said subject has alpha-fetoprotein serum levels of less than 20 μ

g/l.