The Arachidonic Acid Metabolome Reveals Elevation of Prostaglandin E2 Biosynthesis in Colorectal cancer

【作者】 张翠萍； 胡作建； 潘紫月； 季兆东； 曹心怡； 余红秀； 秦雪； 关明；

【机构】 Department of Laboratory Medicine, Shanghai Medical College, Huashan Hospital, Fudan University； Institutes of Biomedical Sciences, Fudan University； Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University； Shanghai Tongji Hospital Affiliated to Tongji University； Shanghai Stomatological Hospital & School of Stomatology, Fudan University；

【摘要】 Arachidonic acid metabolites are a family of bioactive lipids derived from membrane phospholipids. They are involved in cancer progression, but arachidonic acid metabolite profiles and their related biosynthetic pathways remain uncertain in colorectal cancer(CRC). To compare the arachidonic acid metabolite profiles between CRC patients and healthy controls, quantification was performed using liquid chromatography-mass spectrometry-based analysis of serum and tissue samples. Metabolomics analysis delineated the distinct oxidized lipids in CRC patients and healthy controls. Prostaglandin(PGE2)-derived metabolites were increased, suggesting that the PGE2 biosynthetic pathway was upregulated in CRC. The qRT-PCR and immunohistochemistry analyses showed that expression levels of PGE2 synthases, the key protein of PGE2 biosynthesis,was upregulated in CRC, and positively correlated with CD68+ macrophage density and CRC development. Our study indicates that PGE2 biosynthetic pathway is associated with macrophage infiltration and progression of CRC tumors.更多还原

【Abstract】 Arachidonic acid metabolites are a family of bioactive lipids derived from membrane phospholipids. They are involved in cancer progression, but arachidonic acid metabolite profiles and their related biosynthetic pathways remain uncertain in colorectal cancer(CRC). To compare the arachidonic acid metabolite profiles between CRC patients and healthy controls, quantification was performed using liquid chromatography-mass spectrometry-based analysis of serum and tissue samples. Metabolomics analysis delineated the distinct oxidized lipids in CRC patients and healthy controls. Prostaglandin(PGE2)-derived metabolites were increased, suggesting that the PGE2 biosynthetic pathway was upregulated in CRC. The qRT-PCR and immunohistochemistry analyses showed that expression levels of PGE2 synthases, the key protein of PGE2 biosynthesis,was upregulated in CRC, and positively correlated with CD68+ macrophage density and CRC development. Our study indicates that PGE2 biosynthetic pathway is associated with macrophage infiltration and progression of CRC tumors.更多还原