Necroptosis is a kind of programmed necrosis mode that plays a double-edged role in tumor progression. However, the role of necroptosis-related Messenger RNA (mRNA) in predicting the prognosis and immune response of cervical squamous carcinoma and adenocarcinoma (CESC) has not been fully studied. Firstly, the incidence of somatic mutation rate and copy number variation for 74 necroptosis-related mRNAs (NRmRNAs) were analyzed. Secondly, CESC patients were divided into four stable clusters based on the consensus clustering results and analyzed for correlations with a series of clinical factors. Subsequently, a total of 291 The Cancer Genome Atlas samples were randomly divided into either training or validation cohorts. A Cox proportional hazard model consisting of three NRmRNAs (CXCL8, CLEC9A, and TAB2) was constructed by univariate, least absolute shrinkage and selection operator and multivariate COX regression analysis to identify the prognosis and immune response. Its performance and stability were further validated in another testing dataset (GSE44001) from Gene Expression Omnibus database. The results of the receiver operating characteristic curve, principal component analysis, t-SNE, and nomogram indicated that the prognostic model we constructed can serve as an independent prognostic factor. The combination of the prognostic model and the classic TNM staging system could improve the performance in predicting the survival of CESC patients. In addition, differentially expressed genes from high and low-risk patients are screened by R software for functional analysis and pathway enrichment analysis. Besides, single-sample gene set enrichment analysis revealed that tumor-killing immune cells were reduced in the high-risk group. Moreover, patients in the low-risk group are more likely to benefit from immune checkpoint inhibitors. The analysis of tumor immune dysfunction and exclusion scores, M6A-related genes, stem cell correlation and Tumor mutational burden data with clinical information has quantified the expression levels of NRmRNAs between the two risk subgroups. According to tumor immune microenvironment scores, Spearman’s correlation analysis, and drug sensitivity, immunotherapy may have a higher response rate and better efficacy in patients of the low-risk subgroup. In conclusion, we have reported the clinical significance of NRmRNAs for the prognosis and immune response in CESC patients for the first time. Screening of accurate and effective prognostic markers is important for designing a multi-combined targeted therapeutic strategy and the development of individualized precision medicine.

Background:Using bioinformatics analysis and experimental operations, we intend to analyze the potential mechanism of action of capsaicin target gene GATA1 in the treatment of uterine corpus endometrial carcinoma (UCEC) and develop a prognostic model for the disease to validate this model.Methods:By obtaining capsaicin and UCEC-related DR-DEGs, the prognosis-related gene GATA1 was screened. The survival analysis was conducted via establishing high and low expression groups of GATA1. Whether the GATA1 could be an independent prognostic factor for UCEC, it was also validated. The therapeutic mechanism of capsaicin-related genes in UCEC was further investigated using enrichment analysis and immune methods as well as in combination with single-cell sequencing data. Finally, it was validated by cell experiments.Results:GATA1, a high-risk gene associated with prognosis, was obtained by screening. Kaplan-Meier analysis showed that the survival of the high expression group was lower than that of low expression group. ROC curves showed that the prediction effect of the model was good and stable (1-year area under curve (AUC): 0.601; 2-years AUC: 0.575; 3-years AUC: 0.610). Independent prognosis analysis showed that the GATA1 can serve as an independent prognostic factor for UCEC. Enrichment analysis showed that “neuroactive Ligand - receptor interaction and TYPE I DIABETES MELLITUS” had a significant enrichment effect. Single-cell sequencing showed that the GATA1 was significantly expressed in mast cells. Cell experiments showed that the capsaicin significantly reduced the UCEC cell activity and migration ability, as well as inhibited the expression of GATA1.Conclusion:This study suggests that the capsaicin has potential value and application prospect in the treatment of UCEC. It provides new genetic markers for the prognosis of UCEC patients.

Necroptosis, a programmed form of necrotic cell death, plays critical regulatory roles in the progression and metastatic spread of cancers such as cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, there are few articles systematically analyzing the necroptosis-related long non-coding RNAs (NRlncRNAs) correlated with CESC patients. Both RNA-sequencing and clinical data of CESC patients are downloaded from TCGA database in this study. Pearson correlation analysis, least absolute shrinkage, operator algorithm selection and Cox regression model are employed to screen and create a risk score model of eleven-NRlncRNAs (MIR100HG, LINC00996, SNHG30, LINC02688, HCG15, TUBA3FP, MIAT, DBH-AS1, ERICH6-AS1SCAT1, LINC01702) prognostic. Thereafter, a series of tests are carried out in sequence to evaluate the model for independent prognostic value. Gene set enrichment analytic paper, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analytic paper make it clear that immune-related signaling pathways are very rich in the high-risk subgroup. Additionally, the prognostic risk score model is correlated to immune cell infiltration, potential immune checkpoint, immune function, immune micro-environmental and m6A-related gene. Mutation frequency in mutated genes and survival probability trend are higher in the low-risk subgroup in most of test cases when compared to the high-risk subgroup. This study constructs a renewed prognostic model of eleven-NRlncRNAs, which may make some contribution to accurately predicting the prognosis and the immune response from CESC patients, and improve the recognition of CESC patients and optimize customized treatment regimens to some extent.

Endometrial carcinoma is one of the two cancers with rising mortality and morbidity in recent years. In the light of many controversies about its treatment, it is urgent to construct a new prognostic model and to find out new therapeutic directions. As a small drug molecule widely used in clinical treatment and experimental research in China, puerarin has recently been proven to have obvious anti-cancer effects in multiple cancer cells. In this study, bioinformatics analysis and experimental validation were used to explore the potential mechanism of puerarin for endometrial carcinoma and construct a prognostic model. A total of 22 drug-related differential genes were found by constructing a database of drug targets and disease genes. The protein–protein interaction network was constructed for GO and KEGG enrichment analysis to initially explore the potential mechanism of its therapeutic effects. To construct the prognostic model, validation was performed by risk regression analysis and LASSO analysis. Finally, two prognostic genes—PIM1 and BIRC5 were determined to establish high and low risk groups. Kaplan–Meier analysis displayed a higher survival rate in the low-risk group than in the high-risk group. ROC curves indicated the stable and good effect in prediction (one-year AUC is 0.626; two-year AUC is 0.620; three-year AUC is 0.623). The interrelationship between immunity and its disease was explored by immune infiltration analysis. Finally, the potential effect of puerarin on endometrial carcinoma cells was further verified by experiments.

Necroptosis is one of the common modes of apoptosis, and it has an intrinsic association with cancer prognosis. However, the role of the necroptosis-related long non-coding RNA LncRNA (NRLncRNAs) in uterine corpora endometrial cancer (UCEC) has not yet been fully elucidated at present. Therefore, the present study is designed to investigate the potential prognostic value of necroptosis-related LncRNAs in UCEC. In the present study, the expression profiles and clinical data of UCEC patients were downloaded from TCGA database to identify the differentially expressed NRLncRNAs associated with overall survival. A LncRNA risk model was constructed via Cox regression analysis, and its prognostic value was evaluated. We have also further evaluated the relationships between the LncRNA features and the related cellular function, related pathways, immune status, and immune checkpoints m6A-related genes. Seven signatures, including PCAT19, CDKN2B-AS1, LINC01936, LINC02178, BMPR1B-DT, LINC00237, and TRPM2-AS, were established to assess the overall survival (OS) of the UCEC in the present study. Survival analysis and ROC curves indicated that the correlated signature has good predictable performance. The normogram could accurately predict the overall survival of the patients with an excellent clinical practical value. Enrichment analysis of gene sets indicated that risk signals were enriched in several immune-related pathways. In addition, the risk characteristics were significantly correlated with immune cells, immune function, immune cell infiltration, immune checkpoints, and some m6A-related genes. This study has identified seven necroptosis-related LncRNA signatures for the first time, providing a valuable basis for a more accurate prognostic prediction of UCEC.

Background: This study provides a systematic review and meta-analysis of randomized controlled trials, which examined the effect of the selenium supplementation on polycystic ovary syndrome (PCOS). Methods: Confirmed studies related to selenium supplementation and PCOS were searched from the databases of EMBASE, PubMed and Web of Science. Data were reported as weighted mean difference (WMD) or standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis was performed with Stata version 12.0. Results: A total of 389 cases (selenium group n = 195, control group n = 194) were included in this studies. This meta-analysis showed that selenium supplementation has a positive effect on TAC, and supplementation of selenium does not significantly improve the level of BMI, Weight, LDL, HDL, Triglycerides, Total Testosterone, HOMA-IR, NO, GSH, MDA and FPG. Conclusion: Although selenium can improve TAC in PCOS patients, it has no significant effect on BMI, Total Testosterone, et al. In terms of the results of this meta-analysis, it is not recommended for patients with PCOS to use selenium as a regular trace element supplement. Based on the improving effect of selenium on TAC, supplementation of selenium may have a positive effect on improving follicle quality for some PCOS patients who have poor follicle quality caused by oxidative stress or who want to undergo IVF.