Water as a reactant in the differential expression of proteins in cancer

How the abundances of proteins are shaped by tumor microenvironments, such as hypoxic conditions and higher water content compared to normal tissues, is an important question for cancer biochemistry. Compositional analysis of more than 250 datasets for differentially expressed proteins compiled from the literature reveals a higher stoichiometric hydration state in multiple cancer types compared to normal tissue; this trend is also evident in pan-cancer transcriptomic and proteomic datasets from The Cancer Genome Atlas and Human Protein Atlas. These findings support the notion of a basic physicochemical link between increased water content in tumors and the patterns of gene and protein expression in cancer. The generally increased hydration state is juxtaposed with a wide spectrum of carbon oxidation states of differentially expressed proteins, which may be associated with different gene ages, host tissue properties and metabolic features of specific cancer types.