Natriuretic peptide receptor as a biomarker for diagnosis and prognosis of cancer
The invention pertains to biomarkers for clinical detection of malignancies, especially for early detection of cancers. More specifically, this invention pertains to the role of Natriuretic Peptide Receptor A (NPRA) in cancer (e.g., tumor) progression. Thus, the invention includes materials and methods for the detection and prognosis of malignancies. The invention also pertains to methods for treating malignancies.
1. A method for predicting progression of a malignancy and prognosing the malignancy in a human subject diagnosed with the malignancy, comprising:
(a) obtaining a tissue sample suspected of containing malignant cells from the human subject diagnosed with the malignancy;
(b) determining a level of human natriuretic peptide receptor A (NPRA) protein in the tissue sample using an immunohistochemical assay, wherein the human NPRA protein comprises the amino acid sequence of SEQ ID NO:5, and wherein the immunohistochemical assay comprises: (i) contacting the tissue sample with a polyclonal antibody, or fragment thereof, that binds to the human NPRA protein, forming a complex, wherein the polyclonal antibody, or fragment thereof, is capable of binding to an epitope of mouse NPRA protein within the amino acid sequence of SEQ ID NO:3, and (ii) detecting the complex between the polyclonal antibody, or fragment thereof, and the human NPRA protein;
(c) comparing the level determined in (b) with a control NPRA level, wherein a high human NPRA protein level is indicative of an unfavorable prognosis and a low human NPRA protein level is indicative of a favorable prognosis; and
(d) repeating (a)-(c) one or more times over time, to monitor the malignancy over time.
2. The method of claim 1 , wherein the tissue sample comprises tumor cells from the human subject.
3. The method of claim 1 , wherein a favorable prognosis comprises tumor regression and/or longer survival rates relative to patients with unfavorable prognosis.
4. The method of claim 1 , wherein the malignancy is selected from the group consisting of prostate cancer, colon cancer, breast cancer, pancreatic cancer, Merkell cell carcinoma, and gastrointestinal stromal tumor (GIST).
5. The method of claim 1 , wherein the malignancy is colon cancer.
6. The method of claim 5 , further comprising carrying out at least one confirmatory test for the colon cancer.
7. The method of claim 1 , further comprising treating the human subject for the malignancy.
8. The method of claim 1 , further comprising communicating the prognosis to the human subject.
9. The method of claim 1 , wherein the human subject has undergone initiation of a regimen for treatment of the malignancy prior to said obtaining of (a).
10. The method of claim 9 , wherein the control NPRA level is an NPRA level in a tissue sample obtained from the human subject earlier in the treatment regimen.
11. The method of claim 1 , wherein the control NPRA level comprises a plurality of control NPRA levels, and wherein each control NPRA level corresponds to a different stage or grade of the malignancy.
12. The method of claim 11 , wherein the malignancy is prostate cancer, and wherein the stage or grade of the malignancy comprises a Gleason score.
13. The method of claim 1 , wherein the malignancy is prostate cancer.
14. The method of claim 1 , wherein the immunohistochemical assay is a tissue microarray.
15. The method of claim 1 , further comprising cryopreserving the tissue sample prior to said determining.
16. The method of claim 1 , wherein the polyclonal antibody is a rabbit polyclonal antibody.