Bin Yu

EPI-SauriCas9-based mouse ovarian cancer models recapitulating pten deletion in patients

Abstract Ovarian cancer remains a deadly gynecological malignancy, with PTEN loss and TP53 mutations frequently implicated in its progression. However, suitable models for studying ovarian cancers with PTEN and TP53 deletions are rare. Here we develop and validate the mouse ovarian epithelium with Pten and Trp53 deletions (MEPP) model using the EPI-SauriCas9 system. We demonstrate the role of Pten loss in promoting tumorigenicity and metastasis. Single-cell RNA sequencing reveals distinct epithelial subpopulations with varying metastatic potential. MEPP also recapitulates key features of human ovarian cancer, including its immune landscape and therapeutic responses. High-throughput drug screening identifies FK228 and thioguanine as promising therapeutic candidates, both of which show in vivo efficacy and are validated in PTEN -deleted organoids. Together, these results establish MEPP as a platform for studying PTEN- deleted ovarian cancer and provide a strategy for generating clinically relevant tumor models through targeted gene editing.

Tissue Infiltrating Immune Cells as Prognostic Biomarkers in Endometrial Cancer: A Meta-Analysis

Background. The association between tumour-infiltrating immune cells and the prognosis of endometrial cancer (EC) is controversial due to the smaller sample sizes and limited statistical power of the extant studies. We carried out a meta-analysis of the relationship between tumour-infiltrating immune cells and EC survival outcomes. Methods. A literature search in multiple databases was carried out up to December 2019. Pooled hazard ratio (HRs) and 95% confidence intervals (CIs) were calculated by the Z-test to assess the association between infiltrating immune cells and overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), disease-specific survival (DSS), and disease-free survival (DFS). A subgroup analysis was performed based on the localisation of immune cells in tumour parenchyma or stroma, immune markers, and the International Federation of Gynecology and Obstetrics stage. Heterogeneity and publication bias between studies were evaluated by Cochran’s Q-test and Egger regression test, respectively. Results. Seventeen studies were included in the analysis. The pooled HR of OS, PFS, DSS, and DFS indicated that a high CD8+ T cell density was associated with a favorable prognosis in EC patients. A significant relationship was found between a high density of CD45RO+ T cells and a favorable OS in EC patients, but the FoxP3+ T cell density was not associated with either OS or RFS. A high TAM density was associated with a worse PFS. However, a sensitivity analysis indicated that the findings of PFS and DSS in CD8+ T cell and PFS in TAM were not robust results. Conclusion. This is the first meta-analysis of the relationship between tumour-infiltrating immune cells and the prognosis of EC. High CD8+ and CD45RO+ T cell densities in tumours were associated with favorable outcomes in EC patients.