Stoichiogenomics reveal oxygen usage bias, key proteins and pathways associated with stomach cancer

Abstract

Stomach cancer involves hypoxia-specific microenvironments. Stoichiogenomics explores environmental resource limitation on biological macromolecules in terms of element usages. However, the patterns of oxygen usage by proteins and the ways that proteins adapt to a cancer hypoxia microenvironment are still unknown. Here we compared the oxygen and carbon contents ([C]) between proteomes of stomach cancer (hypoxia) and two stomach glandular cells (normal). Key proteins, genome locations, pathways, and functional dissection associated with stomach cancer were also studied. An association of oxygen content ([O]) and protein expression level was revealed in stomach cancer and stomach glandular cells. For differentially expressed proteins (DEPs), oxygen contents in the up regulated proteins were3.2%higherthan that in the down regulated proteins in stomach cancer. A total of 1,062 DEPs were identified; interestingly none of these proteins were coded on Y chromosome. The up regulated proteins were significantly enriched in pathways including regulation of actin cytoskeleton, cardiac muscle contraction, pathway of progesterone-mediated oocyte maturation, etc. Functional dissection of the up regulated proteins with high oxygen contents showed that most of them were cytoskeleton, cytoskeleton associated proteins, cyclins and signaling proteins in cell cycle progression. Element signature of resource limitation could not be detected in stomach cancer for oxygen, just as what happened in plants and microbes. Unsaved use of oxygen by the highly expressed proteins was adapted to the rapid growth and fast division of the stomach cancer cells. In addition, oxygen usage bias, key proteins and pathways identified in this paper laid a foundation for application of stoichiogenomics in precision medicine.

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

“…There are few previous studies of the chemical composition of differentially expressed proteins. Recently, another group has reported higher oxygen contents of proteins in glioma and stomach cancer compared to normal tissue 45, 46. In the present study, a range of differences in carbon oxidation state was documented, from very negative values for prostate cancer to positive values for colorectal, pancreatic, and liver cancer.…”

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer

“…Therefore, up regulation of these pathways might account for the highly use of oxygen elements by up regulated proteins, which lead to the oxygen usage bias in head and neck cancer. Our results were not consistent with resource limitation theory (Zuo et al, 2019). According to the theory, natural selection might bias the usage of the monomers (amino acid or nucleotide) to reduce constrained element costs in the synthesis of biological macromolecules (Elser et al, 2011), when the supply of some elements was constrained in environment.…”

“…holds promises to reveal patterns of differential usages of key elements [e.g. nitrogen (N)] in proteomes (Zuo et al, 2019;Yin et al, 2019). According to the theory of nutrition limitation (Elser et al, 2011), natural selection biases to the usage of the monomers (amino acid or nucleotide) to reduce constrained element costs in the synthesis of biological macromolecules, when supplies of some elements are constrained in the environment (Jun-Ping et al, 2009).…”

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

“…Despite the hypoxic nature of tumors, previous authors did not find significantly lower oxygen contents of proteins in glioma and stomach cancer compared to normal tissue (51,52). Therefore, it is not surprising that in this study a range of differences in carbon oxidation state was documented, from very negative values for prostate cancer to positive values for colorectal, pancreatic, and liver cancer.…”