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PR071/#817  The mechanism study of lipid metabolism disorder to promote lymphovascular space invasion in endometrial cancer by regulating PI3K/Akt axis mediated by ITGB3
  1. Jingyuan Wang,
  2. Xingchen Li and
  3. Jianliu Wang
  1. Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, China, Beijing, China

Abstract

Introduction The aim is to clarify the influence of dyslipidemia on endometrial cancer (EC) and explore the mechanism involved.

Methods The lipid metabolism-related genes and transcriptomics were retrieved from GSEA and TCGA databases. Differentially expressed lipid genes were extracted and a risk signature was identified by using LASSO analysis. A nomogram was established and validated by our own clinical data including 24 EC samples. Furthermore, high-fat diet mice model was established, and the effect of dyslipidemia on the occurrence of lymphovascular space invasion (LVSI) was explored. The transcriptome sequencing technology and the bioinformatics analysis were carried out. Western blot was applied to explore further mechanism.

Results Twelve lipid metabolism-related genes were selected for the development of the risk prediction model. The Kaplan-Meier curve indicated that patients in the low-risk group had better overall survival. Then a nomogram was constructed and validated in external cohort. Oleic acid and palmitic acid were selected for subsequent experiments. The proliferation and migration were promoted by free fatty acids, which might be related to the upregulation of ITGB3. The expression of ITGB3 was related to poor clinicopathological characteristics. The expression of p-PI3K and p-Akt increased under stimulation by free fatty acids; While the upregulation could be inhibited by knocking down ITGB3. Dyslipidemia could promote the development of LVSI in mice, while knocking down ITGB3 could reverse this effect and inhibit the expression of p-PI3K and p-Akt.

Conclusion/Implications The mechanism of dyslipidemia to promote LVSI in EC may have association with the activation of PI3K-Akt signaling pathway mediated by ITGB3.

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