Abstract
BackgroundThe five-year survival rate and therapeutic effect of malignant glioma is low. Identification of key/associated proteins and pathways in glioma is necessary for developing effective diagnosis and targeted therapy of glioma. In addition, Glioma involves hypoxia-specific microenvironment, whether hypoxia restriction influences the stoichioproteomic characteristics of expressed proteins is unknown.MethodsIn this study, we analyzed the most comprehensive immunohistochemical data from 12 human glioma samples and 4 normal cell types of cerebral cortex, identified differentially expressed proteins (DEPs), and researched the oxygen contents of DEPs, highly and lowly expressed proteins. Further we located key genes on human genome to determine their locations and enriched them for key functional pathways.ResultsOur results showed that although no difference was detected on whole proteome, the average oxygen content of highly expressed proteins is 6.65% higher than that of lowly expressed proteins in glioma. A total of 1480 differentially expressed proteins were identified in glioma, including 226 up regulated proteins and 1254 down regulated proteins. The average oxygen content of up regulated proteins is 2.56% higher than that of down regulated proteins in glioma. The localization of differentially expressed genes on human genome showed that most genes were on chromosome 1 and least on Y. The up regulated proteins were significantly enriched in pathways including cell cycle, pathways in cancer, oocyte meiosis, DNA replication etc. Functional dissection of the up regulated proteins with high oxygen contents showed that 51.28% of the proteins were involved in cell cycle and cyclins.ConclusionsElement signature of oxygen limitation could not be detected in glioma, just as what happened in plants and microbes. Unsaved use of oxygen by the highly expressed proteins and DEPs were adapted to the fast division of glioma cells. This study can help to reveal the molecular mechanism of glioma, and provide a new approach for studies of cancer-related biomacromolecules. In addition, this study lays a foundation for application of stoichioproteomics in precision medicine.
Highlights
The five-year survival rate and therapeutic effect of malignant glioma is low
Twelve glioma samples were indicated as yellow triangles, and 4 cerebral cortex cell types were indicated as green dots
We found that glioma samples were separated from normal cerebral cortex samples, which revealed that glioma and cerebral cortex samples were expressional indistinguishable at the overall proteomic level (Fig. 2a), and expressional differences between them could be used for further analysis
Summary
The five-year survival rate and therapeutic effect of malignant glioma is low. Identification of key/ associated proteins and pathways in glioma is necessary for developing effective diagnosis and targeted therapy of glioma. Glioma is the most popular primary malignant tumor in neurosurgery [1], and its five-year survival rate is low, less than 10% [2]. Targeted therapy provides a new method for glioma treatment nowadays [12]. Due to the gradual progression of the disease, the prevention and intervention can be conducted in the early stage of the disease by detecting the target genes, the early diagnosis of glioma can gain precious time for oncologists to effect therapy treatments [13]
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