ADP-ribose polymer - a novel and general biomarker of human cancers of head & neck, breast, and cervix

Abstract

Background:

Poly-ADP-ribosylation (PAR), a reversible post-translational modification of cellular proteins, is involved in various cellular and molecular processes including carcinogenesis (Althaus & Richter, 1987; Jacobson & Jacobson, 1989; Poirier & Moreau, 1992; Boulikas, 1993; Sharan, 2009). ADP-ribose polymer adducts are added onto target cellular proteins by this metabolic process. We hypothesize that a decrease in the concentration of total poly-ADP-ribose adducts of peripheral blood lymphocyte (PBL) proteins strongly correlates with incidence of human cancer. Methods: A novel, sensitive and convenient immunoprobe assay of poly-ADP-ribose adducts of cellular proteins has been employed using slot blots of total PBL lysate (Sharan et al, 1998; 2005; Sharan, 2009). This assay quantifies the metabolic concentration of poly-ADP-ribose adducts of cellular proteins.

Results:

Using the immunoprobe assay, we show a statistically significant (P ≤ 0.001) reduction (~ 42 to 49%) in the level of poly-ADP-ribose adducts of PBL proteins of patients with advanced cancers of head & neck (H & N) region (comprising fourteen distinct types of cancers at different sites), breast and cervix in comparison to healthy controls. Conclusion: These preliminary findings may imply potential utility of the poly-ADP-ribose adducts of PBL proteins as a novel and general biomarker of human cancers with potentials of clinical and epidemiological applications.