Synaptotagmin-like protein 1 is a potential diagnostic and prognostic biomarker in endometrial cancer based on bioinformatics and experiments.

Endometrial cancer (EC) is one of the most common gynecologic malignancies. Identification of potential EC biomarkers is essential to improve the prognosis and development of therapies against EC. Synaptotagmin-like protein 1 (SYTL1), as a small GTPase Rab27 effector, mainly plays a role in vesicle trafficking and cytotoxic granule exocytosis in lymphocytes. However the role of SYTL1 in EC remains uncertain. We performed a comprehensive assessment of the relationship between SYTL1 and patient diagnosis and prognosis by analysis of EC patients' data from TCGA. We employed the LinkedOmics and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to analyze the biological function of SYTL1 in EC. In addition, the correlation between SYTL1 expression and its DNA methylation was performed by using cBioportal, UALCAN, TCGA Wanderer and MethSurv databases. We further assessed the link between SYTL1 and tumor-infiltrating immune cells by using gene set variation analysis (GSVA).Results We found that SYTL1 was highly expressed in EC patients and cell lines. And increased expression of SYTL1 was associated with age, clinical stage, histological type, histological grade and good overall survival (OS).SYTL1 DNA methylation is negatively associated with SYTL1 expression and UCEC patients' OS. SYTL1 expression is closely correlated with immune infiltration. Furthermore, we carried out in vitro experiments to verify the results of bioinformatic analysis.Conclusion Our results demonstrated that the elevation of SYTL1 expression is associated with good OS and SYTL1 might be a potential diagnostic and prognostic marker in EC.

Hypomethylated gene RAC3 induces cell proliferation and invasion by increasing FASN expression in endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is one of the most prevalent gynecological cancers with a 5-year survival rate of 20-60%. Feasible prognostic molecular biomarkers of EC are necessary for accurate prediction of EC prognosis. METHODS: RAC3 is a member of the Rho GTPases. Public databases including Gene Expression Profiling Interactive Analysis (GEPIA2), Tumor Immune Estimation Resource (TIMER), LinkedOmics, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), TISIDB and cBioPortal were employed to analyze the differential expression, clinicopathologic characteristics, functional networks, immune cell infiltrates and genetic alteration of RAC3 in EC patients. RESULTS: RAC3 expression was elevated in EC patients analyzed by TIMER and GEPIA. Overexpression of RAC3 was obviously correlated with clinical stage, histological type, histological grade and DNA hypomethylation. Patients with high RAC3 expression displayed poor overall survival. Functional enrichment analysis showed that RAC3 was involved in translational initiation, DNA replication and mRNA processing. RAC3 expression was negatively associated with infiltrating levels of B cells, CD8 + T cells, macrophages and dendritic cells in EC. Experiments in vitro showed that RAC3 was upregulated in EC tissues and cell lines, and RAC3 induced cell proliferation and invasion by increasing fatty acid synthase (FASN) expression. CONCLUSION: High expression of RAC3iscorrelated with poor prognosis and low infiltration of immune cells in EC. RAC3 promotes cell proliferation and invasion via FASN. These results demonstrate thatRAC3 functions as an EC oncogene and reveal its underlying mechanism in EC progression, suggesting that RAC3 may serve as a potential therapeutic target in EC.