Single‐cell sequencing reveals the heterogeneity and intratumoral crosstalk in human endometrial cancer

Abstract

Background Endometrial cancer (EC) is one of the most common gynecologic malignancies with increasing morbidity. Cell–cell and cell‐matrix interactions within the tumour microenvironment (TME) exert a powerful influence over the progression of EC. Therefore, a comprehensive exploration of heterogeneity and intratumoral crosstalk is essential to elucidate the mechanisms driving EC progression and develop novel therapeutic approaches. Methods 4 EC and 2 normal endometrium samples were applied for single‐cell RNA sequencing (scRNA‐seq) analysis. In addition, we also included the public database to explore the clinical benefits of the single cell analysis. Results 9 types of cells were identified with specific expression of maker genes. Both the malignant epithelial cells and cells comprising the immune microenvironment displayed a high degree of intertumoral heterogeneity. Notably, the proliferation T cells also showed an exhausted feature. Moreover, the malignant cells may induce an immunosuppressive microenvironment through TNF‐ICOS pair. Cancer‐associated fibroblasts (CAFs) were divided into four subsets with distinct characteristics and they maintained frequent communications with malignant cells which facilitating the progression of EC. We also found that the existence of vascular CAF (vCAF) may indicate a worse prognosis for EC patients through integrating TCGA database. Conclusion The TME of human EC remains highly heterogeneous. Out finding that malignant cells interact closely with immune cells and vCAFs identifies potential therapeutic targets.

Integrated multi-omics analyses and functional validation reveal TTK as a novel EMT activator for endometrial cancer

“…Recent applications of single-cell transcriptome analysis in gynecological cancers include elucidating the heterogeneity of the disease, collecting microenvironmental data, elucidating drug resistance mechanisms, and enhancing cancer diagnostic and treatment approaches [ 46 ]. Previous research found that EC cells could be classified into several cell types: epithelial cells, fibroblasts, immune cells, and endothelial cells [ 47 ]. However, an in-depth analysis of epithelial EC cells at the single-cell level is currently lacking.…”

Pan-cancer analysis of the prognostic and immunological role of Fanconi anemia complementation group E

“…These may be related to poor prognosis. Previous studies have shown that fibroblasts maintain frequent communication with cancer cells to promote the development of endothelial cancer ( Yu et al, 2022 ). We also found FANCE is predominantly expressed in fibroblasts and correlated with poor prognosis in endometrial cancer according to scRNA-seq analysis.…”

Fibroblasts as Turned Agents in Cancer Progression

“…The attached fibroblasts are washed and incubated at 37 °C in a tissue culture medium. In addition to generating primary fibroblasts de novo, many fibroblast cell lines from multiple etiologies and organs of origin are available as well from commercial sources [ 61 , 74 , 75 , 76 ].…”

“…Once purified, CAFs and NFs can be analyzed for molecular differences using a variety of standard, population-averaged molecular techniques, including gene expression microarrays and RNAseq, as well as single-cell RNAseq technology [ 69 , 70 , 76 ]. In addition, fibroblasts can be imaged in situ using an array of in situ sensors [ 83 ].…”

“…Cancer cells communicate intensely with cancer-associated fibroblasts in endometrial carcinomas, as well as with other cells in the microenvironment, more so than with each other [ 76 ]. Fibroblasts signal through direct interactions, through fibroblast-secreted cytokines and growth factors and various receptors.…”