Biomarkers for breast cancer
View Patent ↗The present invention provides protein-based biomarkers and biomarker combinations that are useful in qualifying breast cancer status in a patient. In particular, the biomarkers of this invention are useful to classify a subject sample as breast cancer or non-breast cancer. The biomarkers can be detected by SELDI mass spectrometry.
1. A method for diagnosing breast cancer in a subject comprising:
(a) measuring biomarkers human inter alpha trypsin inhibitor heavy chain H4 (ITIH4) fragment 1b (BC-1b), and either C3a-desArgΔ8 (BC-2) or C3a-desArg (BC-3) in serum from the subject with mass spectrometry; and
(b) comparing the measured level of ITIH4 fragment 1b (BC-1b) to a normal control level, and comparing the measured level of C3a-desArgΔ8 (BC-2) or C3a-desArg (BC-3) to a non-cancer control, wherein detection of a reduced level of ITIH4 fragment 1b (BC1-b), and an increased level of either C3a-desArgΔ8 (BC-2) or C3a-desArg (BC-3) correlates with breast cancer, and failure to detect a reduced level of ITIH4 fragment 1b and an increased level of C3a-desArgΔ8 (BC-2) or C3a-desArg (BC-3) correlates with non-breast cancer, wherein the ITIH4 fragment 1b (BC1-b) has an m/z of about 4.6 kD and the C3a-desArgΔ8 (BC-2) consists of SEQ ID NO:2 and the C3a-desArg (BC-3) consists of SEQ ID NO:1.
2. The method of claim 1 , comprising measuring in serum of the subject with mass spectrometry: ITIH4 fragment 1 (BC-1), C3a-desArgΔ8 (BC-2), and C3a-desArg (BC-3), wherein ITIH4 fragment 1 (BC-1) has an m/z of about 4.3 kD.
3. The method of claim 2 further comprising measuring CA15-3 in the serum.
4. The method of claim 1 , wherein said biomarkers are measured by capturing the biomarkers on an adsorbent surface of a SELDI probe and detecting the captured biomarkers by laser desorption-ionization mass spectrometry.
5. The method of claim 1 , wherein the correlating is performed by a software classification algorithm.
6. The method of claim 1 , wherein breast cancer is selected from non-invasive breast cancer and invasive breast cancer.
7. The method of claim 1 , further comprising: (c) managing subject treatment based on the diagnosis.
8. The method of claim 4 , wherein the adsorbent is a IMAC-Ni adsorbent.
9. The method of claim 4 , wherein the adsorbent is a biospecific adsorbent.
10. The method of claim 9 , wherein the biospecific adsorbent comprises an antibody.
11. The method of claim 7 , wherein, if the measurement correlates with breast cancer, then managing subject treatment comprises administering a chemotherapeutic agent or radiation to the subject.
12. The method of claim 7 , further comprising: (d) measuring said biomarkers after subject management and correlating the measurement with disease progression.