Pancreatic cancer remains a highly lethal disease, with no established biomarkers or screening strategy for early detection. Somatic mutation in TP53, primarily in the DNA-binding core region of the protein, results in protein stabilization and autoantibody (AAb) generation. Using a novel method of protein display and detection of serum IgG, we have detected P53-AAb to wild-type (WT) protein in serous ovarian cancer with moderate sensitivity and high specificity, including a subset of cases with false-negative CA 125. In ovarian cancer, we detected rising p53-AAb levels starting 9 months prior to clinical diagnosis, and since the pancreatic cancer has similar, early p53 mutations as serous ovarian cancer, we predict these markers will be present in pancreatic cancer patient sera. Since the AAb were induced by mutated p53, AAb to forms of mutant p53 may improve the assay. We developed a protein microarray expressing the 68 most common p53 mutations that are present in solid tumors. Here, we propose to determine the frequency of WT and mutant-specific p53-AAb, in sera from patients with early and late-stage pancreatic cancers. We will correlate p53-AAb detection with primary and metastatic tumor p53 expression by IHC, and with TP53 mutation status.
There are currently no established biomarkers for the early detection of pancreatic cancer, which remains a highly lethal disease that is almost always detected too late for surgical resection. The goal of this project is to identify blood-based biomarkers measuring autoantibodies to p53 to specifically detect early-stage pancreatic cancer.
| Katchman, Benjamin A; Barderas, Rodrigo; Alam, Rizwan et al. (2016) Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers. Proteomics Clin Appl 10:720-31 |
