Identification of POLQ as a key gene in cervical cancer progression using integrated bioinformatics analysis and experimental validation.

As the most common gynecologic malignancy worldwide, cervical cancer (CC) is a serious hazard to health. Therefore, the present study aimed to identify the key genes in CC progression using integrated bioinformatics analysis and experimental validation. The mRNA microarray GSE63514 and microRNA (miRNA) microarray GSE86100 were obtained from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) in the progression of CC were identified. Thereafter, GO and KEGG functional enrichment analysis, protein­protein interaction (PPI) network and significant subnetworks construction, and miRNA­target regulatory network construction were performed. Based on the results of integrated bioinformatics analysis, the DEGs structural maintenance of chromosomes 4 (SMC4), ATPase family, AAA domain­containing 2 (ATAD2) and DNA polymerase θ (POLQ) were identified as hub genes in the PPI network and were involved in the first significant subnetwork. In addition, these DEGs were predicted to be regulated by miR­106B, miR­17­5P, miR­20A and miR­20B, which were identified as DEMs. Of note, SMC4 and ATAD2 are tumor­promotors in CC. In the present study, small interfering (si)RNAs were used to knock down POLQ expression. Cell Counting Kit­8, Transwell, cell cycle and apoptosis analyses revealed that the downregulation of POLQ restrained cell proliferation, migration and invasion, and promoted apoptosis and the arrest of the cell cycle in the G2 phase. In conclusion, POLQ, which may have a close interaction with SMC4 and ATAD2, may serve a vital role in the progression of CC.

The roles and clinical applications of interleukins in endometrial carcinoma.

As a common malignant tumor of the female reproductive system, endometrial carcinoma (EC) seriously endangers women's health with an increasing incidence. The oncogenesis and progression of cancer are closely linked with immune microenvironment, of which interleukins are the important components. In order to illustrate the roles and clinical applications of interleukins in EC, literature of interleukins and EC were reviewed. Based on the present studies, interleukins play crucial roles in the oncogenesis and development of EC via regulating the proliferation, migration, invasion, angiogenesis, apoptosis, pyroptosis and autophagy of EC as well as the immune function against EC. And some of the interleukins seems to have prospective clinical applications in EC, such as evaluating the risk of tumorigenesis, discriminating the malignancy from benign disorders or normal condition, indicating cancer aggressiveness, predicting the prognosis of patients and serving as the novel therapy. However, there is still a long way to go before the clinical applications of interleukins in EC come into reality. Nevertheless, it is certain that the exploration of interleukins will definitely be of great benefit to the screening, diagnosis and treatment of EC in the future.

The Maternal-Neonatal Outcomes of Twin Pregnancies with Preeclampsia and Their Association with Assisted Reproductive Technology: A Retrospective Study.

Objective: This study aimed to investigate the maternal−neonatal outcomes of twin pregnancies of mothers with preeclampsia and their association with assisted reproductive technology (ART). Methods: A retrospective study on the clinical and maternal−neonatal outcome data of 698 women with twin pregnancies who delivered in our hospital from December 2013 to September 2021 was conducted. Continuous variables were analyzed using a Student's t-test or Wilcoxon rank-sum test. Categorical variables were analyzed using the Chi-square test. The risk factors of twin pregnancies with preeclampsia were analyzed by logistic regression. Results: The rate of twin pregnancy complicated by preeclampsia was 17.62% (123/698). Logistic regression analysis showed that ART increased the risk of preeclampsia in twin pregnancies (AOR: 1.868, 95% CI: 1.187−2.941). Mothers with preeclampsia carrying twins conceived with ART had a higher rate of delivery at gestational week < 34 (29.9% vs. 12.5%) and asphyxia of the neonate at 5 min after delivery (13.4% vs. 1.8%) than those with preeclampsia conceived without ART (p < 0.05). Conclusions: ART increases the risk of preeclampsia in twin pregnancies and the rate of adverse maternal−neonatal outcomes for twin pregnancies with preeclampsia. The policy of single embryo transfer is a method to reduce the adverse pregnancy outcomes of ART.

Endometrial cancer in Lynch syndrome.

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.

The Lung Immune Prognostic Index May Predict the Efficacy of Different Treatments in Patients with Advanced NSCLC: A Meta-Analysis.

BACKGROUND: Our purpose was to evaluate the predictive value of the lung immune prognostic index (LIPI) in patients with advanced non-small cell lung cancer (NSCLC) receiving different treatments. METHODS: A systemic literature search of major databases of medicine was performed to explore the association of LIPI with different therapeutic effects in patients with advanced NSCLC, with overall survival (OS) as the surrogate marker. As such, HR and 95% CI were simultaneously selected to evaluate such an association. RESULTS: A total of 4 studies involving 7,373 patients reported an association of the LIPI score with OS in advanced NSCLC patients. Further sorted by therapeutic regimen, the numbers of patients receiving immune checkpoint inhibitors (ICI), targeted therapy (TT), and chemotherapy (CT) were 3,651, 1,241, and 2,481, respectively. Overall, the good and intermediate LIPI groups (HR = 1.61; 95% CI 1.48-1.75; p < 0.01) showed no heterogeneity (I2 = 0%; p = 0.521), whereas the good and poor LIPI groups (HR = 2.74; 95% CI 2.26-3.33; p < 0.01) had a high heterogeneity (I2 = 67.9%; p = 0.019). For ICI, CT, and TT, the good and intermediate LIPI groups exhibited an HR of 1.70 (95% CI 1.49-1.93; p < 0.01) with I2 = 0% (p = 0.521), an HR 1.49 (95% CI 1.32-1.67; p < 0.01) with I2 = 0% (p = 0.437), and an HR of 1.85 (95% CI 1.45-2.36; p < 0.01) with I2 = 0% (p = 0.382), respectively. The good and poor LIPI groups had an HR of 3.46 (95% CI 2.72-4.39; p < 0.01) with I2 = 51.7% (p = 0.126), an HR of 2.22 (95% CI 1.85-2.66; p < 0.01) with I2 = 20.3% (p = 0.286), and an HR of 3.32 (95% CI 2.53-4.36; p < 0.01) with I2 = 0% (p = 0.703), for ICI, CT, and TT, respectively. CONCLUSIONS: In addition to being a possible prognostic indicator for advanced NSCLC patients receiving ICI, CT or TT, the LIPI may be used to stratify patients in randomized studies. These findings are of great help in deciding on the therapeutic strategy, and more well-designed studies are warranted to further verify them.

The Interaction Between Microorganisms, Metabolites, and Immune System in the Female Genital Tract Microenvironment.

The female reproductive tract microenvironment includes microorganisms, metabolites, and immune components, and the balance of the interactions among them plays an important role in maintaining female reproductive tract homeostasis and health. When any one of the reproductive tract microorganisms, metabolites, or immunity is out of balance, it will affect the other two, leading to the occurrence and development of diseases and the appearance of corresponding symptoms and signs, such as infertility, miscarriage, premature delivery, and gynecological tumors caused by infectious diseases of the reproductive tract. Nutrients in the female reproductive tract provide symbiotic and pathogenic microorganisms with a source of nutrients for their own reproduction and utilization. At the same time, this interaction with the host forms a variety of metabolites. Changes in metabolites in the host reproductive tract are related not only to the interaction between the host and microbiota under dysbiosis but also to changes in host immunity or the environment, all of which will participate in the pathogenesis of diseases and lead to disease-related phenotypes. Microorganisms and their metabolites can also interact with host immunity, activate host immunity, and change the host immune status and are closely related to persistent genital pathogen infections, aggravation of infectious diseases, severe pregnancy outcomes, and even gynecological cancers. Therefore, studying the interaction between microorganisms, metabolites, and immunity in the reproductive tract cannot only reveal the pathogenic mechanisms that lead to inflammation of the reproductive tract, adverse pregnancy outcomes and tumorigenesis but also provide a basis for further research on the diagnosis and treatment of targets.

Identification of key genes and pathways between type I and type II endometrial cancer using bioinformatics analysis.

Endometrial carcinoma (EC) is a common malignant neoplasm of the female reproductive tract. The malignant degree of type II EC is much greater than that of type I EC, usually presenting with a high recurrence rate and a poor prognosis. Therefore, the present study aimed to examine the principal genes associated with the degree of differentiation in type I and type II EC and reveal their potential mechanisms. Differentially expressed genes (DEGs) were selected from the gene expression profiles derived from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In the present study, the KEGG pathway enrichment analysis revealed that 5,962 upregulated DEGs were significantly enriched in the 'p53 signaling pathway' and involved in 'lysine degradation'. In addition, 3,709 downregulated DEGs were enriched in 'pathways in cancer', as well as 'tight junction regulation', the 'cell cycle' and the 'Wnt signaling pathway'. The 13 top hub genes MAPK1, PHLPP1, ESR1, MDM2, CDKN2A, CDKN1A, AURKA, BCL2L1, POLQ, PIK3R3, RHOQ, EIF4E and LATS2 were identified via the protein-protein interaction network. Furthermore, the OncoPrint algorithm from cBioPortal declared that 25% of EC cases carried genetic alterations. The altered DEGs (MAPK1, MDM2, AURKA, EIF4E and LATS2) may be involved in tumor differentiation and may be valuable diagnostic biomarkers. In conclusion, a number of principal genes were identified in the present study that may be determinants of poorly differentiated type II EC carcinogenesis, which may contribute to future research into potential molecular mechanisms. In addition, these genes may help identify candidate biomarkers and novel therapeutic targets for type II EC.

Diagnostic accuracy of preoperative 18F-FDG PET or PET/CT in detecting pelvic and para-aortic lymph node metastasis in patients with endometrial cancer: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to assess the diagnostic accuracy of preoperative 18F-FDG PET or PET/CT in detecting pelvic lymph node (PLN) and para-aortic lymph node (PALN) metastasis in patients with endometrial cancer (EC) in systematic review and meta-analysis format. METHODS: A comprehensive search was performed on PubMed, Cochrane Library, EMBASE, Web of science, SpringerLink and Science Direct for studies reporting the diagnostic value of preoperative 18F-FDG PET or PET/CT in detecting PLN and PALN metastasis had been published up to August 8, 2018. Studies were included if enough data could be extracted for calculation of diagnostic accuracy indices. RESULTS: Nineteen studies (1431 patients in total) were included in the analysis. On a lymph node basis, the overall pooled sensitivity, specificity, AUC and overall diagnostic accuracy (Q* index) of 18F-FDG PET or PET/CT in detecting total lymph node metastasis were 0.68 (95% CI 0.63-0.73), 0.96 (95% CI 0.96-0.97), 0.82, and 0.75, respectively. The corresponding indices for detecting PLN metastasis were 0.61 (95% CI 0.52-0.69), 0.96 (95% CI 0.95-0.97), 0.79, and 0.73, respectively. And the corresponding value for detection of PALN were 0.70 (95% CI 0.58-0.79), 0.92 (95% CI 0.9-0.94), 0.84, and 0.77, respectively. Data based on patients also performed well. CONCLUSIONS: 18F-FDG PET and PET/CT both have excellent diagnostic performance for detecting lymph node metastasis, including PLN and PALN metastasis, in patients with endometrial cancer preoperatively. Though the utility of this method is limited due to its moderate sensitivity, it can help surgeons make better-tailored surgical decision for its high specificity.

Hormonal therapy in uterine sarcomas.

Uterine sarcomas (USs) are a group of rare but aggressive uterine malignancies, accounting for only 1% of the malignant tumors of female reproductive organs. Due to the high rate of recurrence and metastasis, the prognosis of USs is poor. Given the high mortality rate and limited clinical benefit of surgery and adjuvant chemoradiotherapy, hormonal therapy has shown good prospects in recent years. Hormonal agents include progestins, aromatase inhibitors (AIs), and gonadotropin-releasing hormone analogue (GnRH-a). According to the literature, hormonal therapy has been confirmed effective for recurrent, metastatic or unresectable low-grade endometrial stromal sarcoma (LGESS) and hormone receptor positive (ER+/PR+) uterine leiomyosarcoma (uLMS) with favorable tolerance and compliance. Besides, hormonal therapy can also be used in patients with early-staged disease who desire to preserve fertility. However, due to the rarity of USs, the rationale of hormonal therapy is generally extrapolated from data of hormone-sensitive breast cancer, and present studies of hormonal therapy in USs were almost limited to case reports and small-sized retrospective studies. Therefore, further systematic researches and standardized clinical trials are needed to establish the optimal hormonal therapy regimen of USs. Herein, we reviewed the existing studies related to the hormonal therapy in USs in order to provide reference for clinical management in specific settings.

Identification of key genes and pathways in uterine leiomyosarcoma through bioinformatics analysis.

Uterine leiomyosarcoma (uLMS) is a rare but malignant gynaecological tumour with a poor survival outcome. The present study was aimed at identifying the key genes and pathways in the development of uLMS through bioinformatics analysis. To minimize the frequency of false-positive results of the bioinformatics analysis, 3 microarrays including GSE764, GSE64763 and GSE68312 were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were screened out using the online tool GEO2R. Then, Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. Finally, a protein-protein interaction (PPI) network of the DEGs was constructed using Cytoscape, and module analysis was conducted using the plug-in MCODE. A total of 95 DEGs including 21 upregulated genes and 74 downregulated genes were identified. The upregulated DEGs were annotated with 'DNA metabolic process', 'nucleobase-containing compound biosynthetic process' and 'cellular macromolecule biosynthetic process', while the downregulated DEGs were annotated with 'cellular response to chemical stimulus', 'movement of cell or subcellular component' and 'response to inorganic substances'. The results of the PPI network analysis demonstrated that matrix metallopeptidase 9, apolipoprotein E, cyclin E1 and syndecan 1 were the predominant upregulated genes in uLMS. Additionally, the genes in the main module were enriched in 'proteoglycans in cancer', 'p53 signalling pathway' and 'extracellular matrix-receptor interaction'. The key genes and pathways identified in the present study may provide valuable clues for clarifying the molecular mechanism underlying the development of uLMS and demonstrate promise for use as diagnostic markers and therapeutic targets.

Bioinformatics analysis of key differentially expressed genes in well and poorly differentiated endometrial carcinoma.

Endometrial carcinoma (EC) is one of the most common gynecological malignancies. The malignant degree increases between grade (G)1 and G3, and EC of G3 usually presents a high recurrence rate and poor prognosis. Therefore, the present study aimed to examine the principal genes associated with the degree of differentiation in EC. The microarrays GSE17025, GSE24537 and GSE35784, representing data of Type I EC samples of G1 and G3, were downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) and differentially expressed micro (mi)RNAs (DEMs) were identified, followed by functional enrichment analyses and interaction network construction. In total, 83 upregulated and 130 downregulated DEGs with the same expression trends in two mRNA datasets were screened. The upregulated DEGs were primarily enriched in 'mitotic cell cycle process', 'cell cycle process' and 'mitotic cell cycle'; while the downregulated DEGs were enriched in 'cellular component assembly involved in morphogenesis', 'cell projection organization' and 'microtubule­based movement'. From the protein­protein interaction network, DNA topoisomerase IIα, kinesin family member 11, cyclin B1 and BUB1 mitotic checkpoint serine/threonine were identified as foremost hub genes. One module was extracted and involved in 'mitotic cell cycle process' and 'cell cycle process'. Based on the analysis of DEMs and the miRNA­target regulatory network, miRNA­9 may be the most important upregulated DEM, and the DEGs forkhead box P1 and cyclin E1 may serve vital roles in the differentiation of EC. In conclusion, principal genes were identified that may be determinants of the carcinogenesis of poorly differentiated EC, which may facilitate the examination of potential molecular mechanisms. These genes may additionally help identify candidate biomarkers and novel therapeutic targets for poorly differentiated EC.