ABSTRACT
Ferroptosis, a form of programmed cell death induced by excess iron-dependent lipid peroxidation product accumulation, plays a critical role in cancer. However, there are few reports about ferroptosis in endometrial cancer (EC). This article explores the relationship between ferroptosis-related gene (FRG) expression and prognosis in EC patients. One hundred thirty-five FRGs were obtained by mining the literature, retrieving GeneCards and analyzing 552 malignant uterine corpus endometrial carcinoma (UCEC) samples, which were randomly assigned to training and testing groups (1:1 ratio), and 23 normal samples from The Cancer Genome Atlas (TCGA). We established a signature using eight screened FRGs (MDM2, GPX4, PRKAA2, PRNP, SLC11A2, ATP5MC3, PHKG2 and ACO1) related to overall survival using LASSO regression analysis. The samples were divided into low- and high-risk subgroups according to the median risk score. Kaplan-Meier survival curves showed that the low-risk group had better OS. ROC curves showed that this signature performed well in predicting OS (1-, 2-, 3-, and 5-year AUCs of 0.676, 0.775, 0.797, and 0.826, respectively). We systematically analyzed the immune infiltrating profile in UCEC samples from TCGA. Overall, our study identified a novel prognostic signature of 8 FRGs that can potentially predict the prognosis of EC.
Subject(s)
Endometrial Neoplasms/genetics , Endometrial Neoplasms/immunology , Ferroptosis/genetics , Gene Expression Profiling , Lymphocytes, Tumor-Infiltrating/metabolism , Cohort Studies , Databases, Genetic , Female , Gene Expression Regulation, Neoplastic , Genetic Variation , Humans , Molecular Sequence Annotation , Principal Component Analysis , Prognosis , Protein Interaction Maps/genetics , Reproducibility of Results , Risk FactorsABSTRACT
Objective To study the effect of chemically synthesized Nogo-66 receptor ( NgR ) specific small interfering RNA ( siRNA) on nerve regeneration and function of newborn rats after hypoxic-ischemic brain damage ( HIBD) . Methods A total of 50 HIBD newborn rats were set up. They were randomly assigned OR allocated into siNgR group ( n=20 ) , normal saline ( NS ) group ( n=20 ) and HIBD group ( n=10 ) . The rats of siNgR group were given intraventricular injection of siNgR and transfection reagents ( 10μl ); the rats of NS group were given intraventricular injection of NS and transfection reagents (10μl);and the rats of HIBD group had no intervention. In addition to these three groups, there is another group, sham-operated group ( n=10 ) . The rats of sham-operated group were sham-operated ( common carotid artery was isolated but not ligated) and did not receive hypoxia-ischemia processing and intraventricular injection. Utilize water maze experiment to analyze the rats' escape time. The levels of NgR and GAP-43 protein in rats' brains were measured by immunohistochemistry and image analysis. Results RT-PCR gel electrophoresis results showed that the NgR cDNA stripe of siNgR group was not obvious, but the stripe of NS group was clear. At the same time, the GAPHD cDNA bands of the above two groups were both clear. There were more NgR positive immune reaction products ( brown particles) in NS group than in siNgR group. The number of GAP-43 positive cells by immunohistochemistry in sham-operated group, HIBD group, NS group and siNgR group was (33. 24±1. 32), (20. 14±1. 24), (18. 73±1. 41) and (28. 06±1. 78), respectively. The number of sham-operated group and siNgR group was greater than HIBD group and NS group ( P＜0. 05 ) . There was no statistical significant difference for the number of GAP-43 positive cells between sham-operated group and siNgR group ( P＞0. 05 ) . Water maze experiment results showed that the newborn rats ' average escape time ( s ) of HIBD group ( 58. 1 ± 10. 3,47. 2±10. 1, 42. 5±7. 6) was obviously longer than sham-operated group (34. 2±5. 6, 25. 7±6. 2, 21. 2±8. 1), and the difference was statistically significant (P＜0. 05). However, the average escape time of siNgR group (37. 5±9. 8, 29. 1±9. 8, 27. 2±9. 3) was obviously shorter than HIBD group and NS group (60. 7±5. 2, 49. 1±9. 9, 45. 3±9. 3), (P＜0. 05). Conclusions Chemically synthesized specific siRNA had the potential to interference the expression of NgR in the brain of newborn rats, and to a certain extent, could promote the nerve regeneration and neural functional recovery of rats.
