Proteomic indicators of oxidation and hydration state in colorectal cancer

ABSTRACT New integrative approaches are needed to harness the potential of rapidly growing datasets of protein expression and microbial community composition in colorectal cancer (CRC). Chemical and thermodynamic models offer theoretical tools to describe populations of biomacromolecules and their relative potential for formation in different microenvironmental conditions. The average oxidation state of carbon (Z C ) can be calculated as an elemental ratio from the chemical formulas of proteins, and water demand per residue is computed by writing the overall formation reactions of proteins from basis species. Using reported results from clinical proteomic studies and microbial community profiling, many datasets exhibit higher mean Z C or of proteins in carcinoma or adenoma compared to normal tissue. Microbial protein compositions have lower Z C in bacteria enriched in fecal samples from cancer patients. In thermodynamic calculations, the potential for formation of the cancer-related proteins is energetically favored by changes in the chemical activity of H 2 O and fugacity of O 2 that reflect the compositional differences. The compositional analysis suggests that a systematic shift in chemical composition is an essential feature of the cancer proteome, and the thermodynamic descriptions show that the observed proteomic transformations could be promoted by microenvironments shifted toward more oxidizing conditions and increased hydration levels.