Methods for detection, staging, and surveillance of colorectal adenomas and carcinomas
This invention provides minimally invasive methods, reagents, diagnostic and prognostic markers useful for staging, prognosis and surveillance of colorectal cancers, and therapeutic intervention in individuals with colorectal cancers, or individuals who may be susceptible to developing colorectal cancers.
1. A method for treating a colorectal cancer patient in need thereof with a neoadjuvant therapy after identifying the patient as having local or regional colorectal cancer, the method comprising:
(a) assaying a biosample from the patient for the plurality of protein biomarkers comprising CD44, C-reactive protein, inter-alpha trypsin inhibitor, heavy chain H3vitamin D binding protein; and dipeptidyl peptidase 4, wherein the protein biomarkers are present in an individual without cancer at reference levels; and
(b) detecting levels of the plurality of the protein biomarkers in the biosample;
wherein the colorectal cancer patient is treated with neoadjuvant therapy when the levels of these protein biomarkers from the patient′ biosample is higher than the reference protein biomarker levels from individuals without colorectal cancer.
2. The method of claim 1 , wherein the biosample is assayed by a method comprising:
(a) selecting one or more detectably labeled synthetic peptides with homology to one or a plurality of the protein biomarkers;
(b) combining the detectably labeled synthetic peptides with the biosample; and
(c) subjecting the combination to a physical separation method.
3. The method of claim 2 , wherein the physical separation method is liquid chromatography.
4. The method of claim 2 , wherein the synthetic peptides are isotopically labeled.
5. The method of claim 1 , wherein detecting the level of one or a plurality of protein biomarkers comprises quantification of the concentration of protein biomarkers in the biosample.
6. The method of claim 1 , wherein the assaying step comprises an immunologic assay.
7. The method of claim 6 , wherein said immunologic assay comprises an enzyme-linked immunosorbent assay.
8. The method of claim 1 , wherein the detecting step comprises mass spectrometry.
9. The method of claim 1 , wherein the biosample is from a subject post-polypectomy, post-colectomy, or after other therapeutic intervention.
10. The method of claim 9 , wherein the biosample is collected within 1 month, 2 months, 3 months, 4 months, 5 months or 6 months post-polypectomy.
11. The method of claim 9 , wherein the biosample is collected within one year or two years post-polypectomy.
12. The method of claim 9 , further comprising the step of (c) identifying an individual having a polyp following a polypectomy or other therapeutic intervention by comparing the level of the one or a plurality of the protein biomarkers in the biosample to a reference level of said one or a plurality of protein biomarkers.
13. The method of claim 1 , wherein the method is non-invasive.