The incidence and mortality rates of endometrial cancer are increasing during recent years. CA125 (gene symbol MUC16) is a well-known diagnostic and prognostic serum marker of endometrial cancer. High serum CA125 level is associated with poor prognosis. MUC16 is one of the most frequently mutated genes in endometrial cancer. However, the potential relationship and underlying mechanism between MUC16 mutations and endometrial cancer patients’ prognosis and disease progression remain unclear. In present study, we analyzed the whole exome sequencing data, RNA sequencing data and patients’ clinical information in TCGA database and demonstrated that MUC16 mutational status was an independent prognostic factor for endometrial cancer patients. Patients with somatic MUC16 mutations had a prolonged overall survival time. MUC16 mutations promoted patients’ antitumor immune responses. Cytotoxic immune cells mediated pathways were enriched in endometrial cancer samples with MUC16 mutations. Elevation of two pathways, NO2-dependent IL 12 pathway in NK cells and T cytotoxic cell surface molecules, significantly correlated with a higher rate of MUC16 mutations and a significantly favorable patients’ prognosis. An increased level of cytotoxic T lymphocytes, not NK cells, infiltration was observed in the tumor microenvironment of patients with MUC16 mutations. High expression of molecular markers of T cells and CD8⁺ T cells associated with a higher rate of MUC16 mutations and a better patients’ prognosis. These findings may provide deeper insight into potential endometrial cancer immunotherapy approaches.

The increasing incidence rate and decreasing patients' five-year survival rate for endometrial cancer (EC) in recent decades highlight the necessity for further investigation of the molecular characteristics involved in cancer initiation and progression. In this study, we found that the pathways associated with mitotic cell cycle were enriched in primary EC samples versus normal endometrial samples through analyzing RNA-seq data of The Cancer Genome Atlas (TCGA). The messenger RNA (mRNA) expression of three activator E2Fs (E2F1, E2F2, and E2F3) and their target genes increased significantly in EC samples. Additionally, the high transcriptional activity of activator E2Fs was associated with poor survival, advanced clinical stage, high histologic grade, and aggressive histological type. We further demonstrated that E2Fs hyperactivation correlated with DNA hypomethylation and high cyclin-dependent kinase 4 (CDK4) expression. Moreover, abemaciclib, a selective CDK4 inhibitor, significantly inhibited the proliferation rates of human EC cell lines in vitro. And, abemaciclib also obviously inhibited EC cell growth in nude mice model. Collectively, our data suggest that the misregulation of CDK4/RB/E2Fs axis is associated with EC oncogenesis, and abemaciclib is a potential targeted drug for EC.

Background: Endometriosis is a chronic systemic disease, whose classic symptoms are pelvic pain and infertility. This disease seriously reduces the life quality of patients. The pathogenesis, recognition and treatment of endometriosis is still unclear, and cannot be over emphasized. The aim of our study was to investigate the potential biomarker of endometriosis for the mechanism and treatment. Methods: Using GSE11691, GSE23339 and GSE5108 datasets, differentially expressed genes (DEGs) were identified between endometriosis and normal samples. The functions of DEGs were reflected by the analysis of gene ontology (GO), pathway enrichment and gene set enrichment analysis (GSEA). The LASSO regression model was performed to identify candidate biomarkers. The receiver operating characteristic curve (ROC) was used to evaluate discriminatory ability of candidate biomarkers. The predictive value of the markers in endometriosis were further validated in the GSE120103 dataset. Then, the expression level of biomarkers was detected by qRT-PCR and Western blot. Finally, the relationship between candidate biomarker expression and immune infiltration was estimated using CIBERSORT. Results: A total of 42 genes were identified, which were mainly involved in cytokine–cytokine receptor interaction, systemic lupus erythematosus and chemokine signaling pathway. We confirmed PDLIM3 was a specific biomarker in endometriosis (AUC = 0.955) and validated in the GSE120103 dataset (AUC = 0.836). The mRNA and protein expression level of PDLIM3 in endometriosis tissue was significantly higher than normal. Immune cell infiltration analysis revealed that PDLIM3 was correlated with M2 macrophages, neutrophils, CD4+ memory resting T cells, gamma delta T cells, M1 Macrophages, resting mast cells, follicular helper T cells, activated NK cells, CD8+ T cells, regulatory T cells (Tregs), naive B cells, plasma cells and resting NK cells.

Pregnancy, from insemination to parturition, is a highly complex but well-orchestrated process that requires various organs and systems to participate. Immune system and neuroendocrine system are important regulators in healthy pregnancy. Dozens of neuroactive factors have been detected in human placenta, whether they are locally secreted or circulated. Among them, some are vividly studied such as corticotropin-releasing hormone (CRH), human chorionic gonadotropin (hCG), transforming growth factor-β (TGF-β), progesterone and estrogens, while others are relatively lack of research. Though the neuroendocrine-immune interactions are demonstrated in some diseases for decades, the roles of neuroactive factors in immune system and lymphocytes during pregnancy are not fully elucidated. This review aims to provide an interdisciplinary view on how the neuroendocrine system mediate immune system during pregnancy process.

Purpose The aim of this study was to compare patterns of recurrence in 2009 FIGO Stage IB-IIA (T1bN0M0-T2aN0M0) cervical cancer patients with cN0 and cN1. Methods The epidemiological and clinical data of 1352 patients who had undergone radical hysterectomy and systematic lymphadenectomy with cervical cancer treated from January 2008 to April 2019 at a tertiary teaching hospital were retrospectively collected. The primary aim was to discover the lymph node status-dependent patterns and time of recurrence. Results Tumor recurrence and death were significantly less common in patients with cN0 than cN1. In addition, the length of time to recurrence (median 60 months cN0 vs. 43 months cN1, p < 0.001) and death (median 84 months cN0 vs. 68 months cN1 p < 0.001) were significantly longer in cN0 versus cN1 patients. The cumulative rate of relapse also showed a significant difference between cN0 and cN1 groups, especially the 1-year relapse rate (2.14% vs. 10.78%). Of the patients who recurred, there was no difference in number of recurrent sites between cN0 and cN1 groups (solitary metastases:35.8% of cN0 and 35.6% of cN1; multiple metastases: 64.2% of cN0 and 64.4% of cN1). Similarly, there was no statistical difference in recurrence sites of cervical cancer between cN0 and cN1 groups based on three categories, (p = 0.646). However, in the six categories, patients' vaginal vaults with negative lymph nodes were more prone to recurrence, while the distribution of other recurrence sites showed no significant difference between the two groups. Conclusions There is a significant improvement of relapse-free survival in the cN0 group, and the recurrence time of cN0 patients is significantly delayed than cN1 group. However, except for the risk of metastasis of the vaginal vault, the site of relapse remains similar.