Characterization of tumour microenvironment reprogramming reveals invasion in epithelial ovarian carcinoma

Journal of ovarian research(2023)

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摘要
Patients with epithelial ovarian carcinoma (EOC) are usually diagnosed at an advanced stage with tumour cell invasion. However, identifying the underlying molecular mechanisms and biomarkers of EOC proliferation and invasion remains challenging. Herein, we explored the relationship between tumour microenvironment (TME) reprogramming and tissue invasion based on single-cell RNA sequencing (scRNA-seq) datasets. Interestingly, hypoxia, oxidative phosphorylation (OXPHOS) and glycolysis, which have biologically active trajectories during epithelial mesenchymal transition (EMT), were positively correlated. Moreover, energy metabolism and anti-apoptotic activity were found to be critical contributors to intratumor heterogeneity. In addition, HMGA1, EGR1 and RUNX1 were found to be critical drivers of the EMT process in EOC. Experimental validation revealed that suppressing EGR1 expression inhibited tumour cell invasion, significantly upregulated the expression of E-cadherin and decreased the expression of N-cadherin. In cell components analysis, cancer-associated fibroblasts (CAFs) were found to significantly contribute to immune infiltration and tumour invasion, and the accumulation of CAFs was associated with poorer patient survival. We revealed the molecular mechanism and biomarkers of tumour invasion and TME reprogramming in EOC, which provides effective targets for the suppression of tumour invasion.
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关键词
epithelial ovarian carcinoma,tumour microenvironment reprogramming
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