Identification of Lupus-Associated Genes in the Pathogenesis of Pre-eclampsia Via Bioinformatic Analysis.

Pre-eclampsia (PE) is a severe pregnancy complication that is more common in patients with systemic lupus erythematosus (SLE). Although the exact causes of these conditions are not fully understood, the immune system plays a key role. To investigate the connection between SLE and PE, we analyzed genes associated with SLE that may contribute to the development of PE. We collected 9 microarray data sets from the NCBI GEO database and used Limma to identify the differentially expressed genes (DEGs). In addition, we employed weighted gene co-expression network analysis (WGCNA) to pinpoint the hub genes of SLE and examined immune infiltration using Cibersort. By constructing a protein-protein interaction (PPI) network and using CytoHubba, we identified the top 20 PE hub genes. Subsequently, we created a nomogram and conducted a receiver operating characteristic (ROC) analysis to predict the risk of PE. Our analysis, including gene set enrichment analysis (GSEA) and PE DEGs enrichment analysis, revealed significant involvement in placenta development and immune response. Two pivotal genes, BCL6 and MME, were identified, and their validity was confirmed using 5 data sets. The nomogram demonstrated good diagnostic performance (AUC: 0.82-0.96). Furthermore, we found elevated expression levels of both genes in SLE peripheral blood mononuclear cells (PBMCs) and PE placental specimens within the case group. Analysis of immune infiltration in the SLE data set showed a strong positive correlation between the expression of both genes and neutrophil infiltration. BCL6 and MME emerged as crucial genes in lupus-related pregnancies associated with the development of PE, for which we devised a nomogram. These findings provide potential candidate genes for further research in the diagnosis and understanding of the pathophysiology of PE.

Predictive Factors for the Common Adverse Maternal and Fetal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus.

Objectives: This study aimed to evaluate the outcomes of pregnancy in patients with systemic lupus erythematosus (SLE). It focused on identifying clinical and laboratory markers that could predict the common adverse pregnancy outcomes (APOs) after 20 weeks of gestation, namely preeclampsia (PE) and preterm birth (PTB) in them. Methods: Pregnant SLE women who delivered at the study center from 2010 to 2023 were retrospectively analyzed. Categorical variables were evaluated using the chi-square test or Fisher's exact test, while continuous variables underwent Mann-Whitney U testing. Stepwise regression was used to assess the predictors of pregnancy outcomes. Results: The study enrolled 445 pregnancies in 408 women diagnosed with SLE. Of these, 202 pregnancies (45.4%) resulted in at least one APO. Disease flare-ups, hypertension, and proteinuria during the first trimester were primary predictors of at least one APO and PTB. The most frequently recorded maternal adverse outcome was PE (14.6%), while PTB accounted for 32.6% of fetal adverse outcomes. Multivariate regression analysis identified hypertension, history of PE, associated antiphospholipid syndrome (APS), proteinuria, and low serum C4 in the first trimester as independent risk factors for PE. Regular follow-ups at our center correlated with lower risks of APOs, PE, and PTB. APS also emerged as a risk factor for PTB, whereas the use of hydroxychloroquine (HCQ) during pregnancy seemed to protect against PTB. Conclusion: For pregnancies complicated by SLE, we recommend early pregnancy screening for proteinuria-even in the absence of lupus nephritis-as well as continued use of HCQ and routine prenatal care throughout pregnancy.

Prognosis of uterine and extrauterine low-grade endometrial stromal sarcoma: an observational cohort study.

OBJECTIVE: Little is known about the survival differences between uterine and extrauterine low-grade endometrial stromal sarcoma (LGESS). Survival outcomes, consisting of disease-free survivals and overall survivals (OS), were compared in these two entities. METHODS: From February 2012 to June 2019, all primary LGESS cases and LGESS cases with first recurrence in the study center were reviewed. The clinicopathological characteristics and survival outcomes of extrauterine and uterine LGESS patients were compared for both primary and recurrent diseases. RESULTS: During the study period, 143 patients with primary LGESS and 56 patients with recurrent LGESS were included and followed up to 1 June 2020, among whom 8 (5.6%) and 10 (17.8%) patients were identified as having extrauterine LGESS. Patients with primary and recurrent extrauterine LGESS had similar clinicopathological characteristics to those of patients with uterine LGESS. In primary or in recurrent LGESS cases, in univariate analysis, patients with uterine and extrauterine LGESS had similar disease-free intervals after the last treatment, and they also had similar OSs after the diagnosis. Ovarian preservation led to significantly increased recurrence for primary LGESS [hazard ratio (HR) 4.9, 95% CI: 2.3-10.1, P <0.001) and repeated recurrence for recurrent LGESS (HR 3.1, 95% CI: 1.3-7.3, P =0.009). Surgical treatment for recurrent LGESS decreased repeated recurrence after the first recurrence (HR 0.2, 95% CI: 0.1-0.7, P =0.006). No factors were found to be associated with the OS of primary or recurrent LGESS. CONCLUSION: The clinical characteristics and survival outcomes of extrauterine LGESS are similar to those of uterine LGESS. Surgery is the treatment of choice for recurrent LGESS. Ovarian preservation is detrimental to disease-free survival but not to OS in both uterine and extrauterine LGESS.

The prognosis of recurrent low-grade endometrial stromal sarcoma: a retrospective cohort study.

BACKGROUND: The prognosis of recurrent low-grade endometrial stromal sarcoma (LGESS) is little known. This study was to investigate the survival outcomes of a cohort of patients with recurrent LGESS. METHODS: Patients with primary LGESS diagnosed and treated for first recurrence confirmed by histology in the study center from February 2012 to June 2019 were retrospectively included. The progression-free interval (PFI) after the last treatment for first recurrence and overall survival (OS) since the diagnosis of first recurrence, which were followed up to June 1, 2020, were compared between groups of various therapy modalities. RESULTS: Fifty-six patients were included, and 43 patients (76.8%) had definite follow-up outcomes. The 5-year PFI and OS rates were 30.0% (95% confidence interval [95% CI] 29.2-30.8) and 75.0% (68.0-82.0), respectively. In univariate analysis, only fertility-sparing treatment, ovarian preservation and surgical treatment had a significant impact on the PFI (hazard ratio [HR] 4.5, 3.1, and 0.2; 95% CI 1.5-13.1, 1.3-7.3, and 0.1-0.7; and p = 0.006, 0.009 and 0.006, respectively), but no factor was found to be associated with increased mortality risk. After adjusted with hormone treatment or chemotherapy, surgical treatment had significant effectiveness on OS (HR 0.3 and 0.3, 95% CI 0.1-1.0 and 0.1-1.0, p = 0.045 and 0.049, respectively). None of the patients with fertility-sparing treatment had successful conception, and all experienced repeated relapse. CONCLUSION: For patients with recurrent LGESS, fertility-sparing treatment or ovarian preservation should not be provided. Surgery is the treatment of choice, and hormone treatment and/or chemotherapy was effective for the survival benefits of surgical treatment.