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.
Highlights
As one of the most common gastrointestinal malignancies in the world, stomach cancer is still a leading cause of death in less developed countries[1]
Huge proteomic data based on immunohistochemical method offered by Human Protein Atlas project (HPA)[36] are available, which provides us an opportunity to study the relationship between element content and protein expression level in hypoxia stomach cancer, and offers us a possibility to screen key proteins associated with stomach cancer from the proteome perspective
Oxygen contents of all proteins expressed in stomach cancer and normal stomach glandular cells
Summary
As one of the most common gastrointestinal malignancies in the world, stomach cancer is still a leading cause of death in less developed countries[1]. A study of 232 patients in China showed that the post-treatment survival rates after 1, 3 and 5 years were 98.90%, 80.20% and 43.30%, respectively. Stoichiogenomics provides a new method for biology sequence analyses, especially on how environmental constraints affect element contents and expression levels of biological macromolecules[29]. Whether a hypoxic microenvironment lessens the oxygen contents in the expressed proteins in stomach cancer is still unknown. Huge proteomic data based on immunohistochemical method offered by Human Protein Atlas project (HPA)[36] are available, which provides us an opportunity to study the relationship between element content and protein expression level in hypoxia stomach cancer, and offers us a possibility to screen key proteins associated with stomach cancer from the proteome perspective
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