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Background: To compare the impact of surgical approach on progression free survival (PFS) stratified by histologic type in women diagnosed with stage IA endometrial cancer. Methods: Myometrial invasion is classified into no myometrial invasion, <50% and ≥50%, with only no myometrial invasion and <50% are included in stage IA patients. A retrospective study is designed by collecting data from women diagnosed as stage IA endometrial cancer from January 2010 to December 2019 in a tertiary hospital. A propensity score is conducted for 1:1 matching in the low-risk histologic patients. Progression free survival and disease-specific survival data are evaluated by the Kaplan–Meier method and compared by the log-rank test in both the whole population and the matched-pair groups. A sub-group analysis is performed to figure out risk factors associated with the effect of surgical approach on PFS and disease-specific survival (DSS). Results: 534 (84.49%) low-risk histologic endometrial cancer women, with 389 (72.85%) operated by minimally invasive surgery and 145 (27.15%) by open approach, and 98 (15.51%) high-risk histology, with 71 (72.45%) by laparoscopy and 27 (27.55%) by open surgery, are included. Compared to open surgery, laparoscopy results in lower progression free survival in low-risk patients before and after matching (p = 0.039 and p = 0.033, respectively), but shows no difference in high-risk patients (p = 0.519). Myometrial invasion is associated with lower progression free survival in laparoscopy in low-risk histology (p = 0.027). Conclusion: Surgical approaches influence progression free survival in stage IA low-risk histologic diseases, especially in those with myometrial invasion, but not in high-risk histologic endometrial cancer. [ABSTRACT FROM AUTHOR]

Although many studies have confirmed the relationship between obesity and endometrial cancer (EC), the molecular mechanism between obesity and EC progression has not been elucidated. Overexpression of fat mass and the obesity associated protein FTO leads to weight gain, although recently it has been discovered that FTO can serve as a demethylase which erases N6-methyladenosine (m6A) modification and regulates the metabolization of mRNAs. In this study, we found high expression of FTO in metastatic EC and that this action promote both metastasis and invasion in vivo and in vitro. Mechanistically, FTO can catalyse demethylation modification in 3ʹUTR region of HOXB13 mRNA, thereby abolishing m6A modification recognition with the YTHDF2 protein. Decreasing HOXB13 mRNA decay and increasing HOXB13 protein expression was accompanied by WNT signalling pathway activation and the expression of downstream proteins, leading to tumour metastasis and invasion. We also found the WNT signalling pathway inhibitor ICG-001 can block HOXB13 gene-induced tumour metastasis, therefore ICG-001 may be a promising molecular intervention. This study provides insight into the relationship between obesity and the pathogenesis of endometrial cancer while highlighting future areas of research. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is a fatal female reproductive tumor. Bioinformatic tools are increasingly developed to screen out molecular targets related to EC. In this study, GSE17025 and GSE40032 were obtained from Gene Expression Omnibus (GEO). "limma" package and Venn diagram tool were used to identify hub genes. FunRich was used for functional analysis. Retrieval of Interacting Genes Database (STRING) was used to analyze protein‐protein interaction (PPI) complex. Cancer Genome Atlas (TCGA), GEPIA, immunohistochemistry staining, and ROC curve analysis were carried out for validation. Univariate and multivariate regression analyses were performed to predict the risk score. Compound muscle action potential (CMap) was used to find potential drugs. GSEA was also done. We retrieved seven oncogenes which were upregulated and hypomethylated and 12 tumor suppressor genes (TSGs) which were downregulated and hypermethylated. The upregulated and hypomethylated genes were strikingly enriched in term "immune response" while the downregulated and hypermethylated genes were mainly focused on term "aromatic compound catabolic process." TCGA and GEPIA were used to screen out EDNRB, CDO1, NDN, PLCD1, ROR2, ESPL1, PRAME, and PTTG1. Among them, ESPL1 and ROR2 were identified by Cox regression analysis and were used to construct prognostic risk model. The result showed that ESPL1 was a negative independent prognostic factor. Cmap identified aminoglutethimide, luteolin, sulfadimethoxine, and maprotiline had correlation with EC. GSEA results showed that "hedgehog signaling pathway" was enriched. This research inferred potential aberrantly methylated DEGs and dysregulated pathways may participate in EC development and firstly reported eight hub genes, including EDNRB, CDO1, NDN, PLCD1, ROR2, ESPL1, PRAME, and PTTG1 that could be used to predict EC prognosis. Aminoglutethimide and luteolin may be used to fight against EC. [ABSTRACT FROM AUTHOR]

The expression of homeobox gene DLX4 has been verified in some tumors, but not in endometrial cancer. We found that expression of DLX7 , a splicing isoform of DLX4 , did not show any significant difference in expression between endometrial cancer and endometrium. However, BP1 , another splicing isoform of DLX4 , was highly expressed in endometrial cancer, and its expression was positively correlated with patient prognosis, cancer pathological grade, tumor invasion and metastasis. Lentiviral-mediated expression of BP1 in HEC-1-B cells accelerated the cell cycle progression from G0/G1 into S phase, and promoted cell proliferation and migration both in vitro and in vivo. Real-time PCR and western blotting showed that the expression levels of p15, p21 and E-cadherin significantly decreased, and levels of cyclinD1 and MMP-2 increased in endometrial cancer cells. In conclusion, our results demonstrate that high expression of BP1 is associated with poor prognosis in patients with endometrial cancer and promotes cell proliferation and migration. • BP1 is significantly overexpressed in endometrial cancer. • BP1 expression correlates with cancer pathological grade, tumor invasion and metastasis, and prognosis. • BP1 overexpression reduced G0/G1 cells and promoted proliferation and migration. • BP1 expression promoted cyclinD1 and MMP-2 expression and reduced p15, p21 and E-cadherin expression. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of preoperative hysteroscopy on progression‐free survival (PFS) and disease‐specific survival (DFS), and to explore the factors which contribute to poor clinical outcomes between hysteroscopy and dilation and curettage (D&C) in endometrial cancer (EC). Methods: A retrospective study was designed by collecting data from women diagnosed with EC through hysteroscopy or D&C from January 2010 to December 2019 in a tertiary hospital in China. A propensity score was used for 1:1 matching of advanced stage patients. Univariate and multivariate analysis were conducted to determine whether hysteroscopy was a prognostic factor in EC and to identify factors associated with its impact on PFS and DFS in different subgroups. Results: Overall, 543 and 272 women who underwent D&C and hysteroscopy, respectively were included. Compared to D&C, preoperative hysteroscopy was related to reduced PFS and DFS, with a hazard ratio (HR) of 1.904 and 3.905, respectively. Hysteroscopy contributed to an increased risk of positive wash cytology (48.27% vs 24.13%), recurrence (48.28% vs 20.69%) and shorter PFS after matching in FIGO Stage I–IV EC, while there was no significance in positive ascites cytology (14.04% vs 13.45%), PFS and DFS in FIGO Stage I EC. Conclusions: Hysteroscopy was an independent predictive factor for poor prognosis in EC. Hysteroscopy appeared to be a safe diagnostic method as D&C in FIGO Stage I EC but was a risk factor for increased recurrence and reduced PFS in advanced stage disease. Its impact on DFS is uncertain. Synopsis: Preoperative hysteroscopy procedure was associated with increased risk of recurrence and shorter PFS in advanced endometrial cancer. [ABSTRACT FROM AUTHOR]