Systematic Analysis of Tumor Microenvironment Patterns and Oxidative Stress Characteristics of Endometrial Carcinoma Mediated by 5-Methylcytosine Regulators.

As a widely distributed RNA methylation modification, m5C is involved in the regulation of tumorigenesis. Nevertheless, its fundamental process is not clear. This research sought to examine the genetic properties of the 5-methylcytosine (m5C) regulator in endometrial carcinoma, as well as the prognostic significance and impact of m5C regulators on oxidative stress. Therefore, the TCGA-UCEC data set was used to explore the characteristics of 17 RNAm5C-related genes in the transcriptome, genome, and regulatory network. The subtypes of RNAm5C in UCEC were identified based on the expression levels of 17 RNAm5C-related genes. The prognosis of RNAm5C-2 was significantly better than that of RNAm5C-1. Then, we examined the differences (variations) across various subtypes in terms of immune cell infiltration (ICI) as well as the expression of immune-related signal markers. The findings demonstrated that there were distinct variations in the infiltration level of immune cells in each subtype, which may be the reason for the differences in the prognosis of each subtype. In addition, the differentially expressed genes (DEGs) among RNAm5C subtypes of different UCEC tumors were identified, and the DEGs significant for survival were screened. After obtaining 34 prognostic genes, the dimensionality was reduced to construct an RNA methylation score (RS). As per the findings, RS is a more accurate marker for determining the prognosis for patients with endometrial cancer. The RS was used to categorize UCEC tumor samples, and these results led to the formation of high-score and low-score groups. The patients in the group with a high-RNA methylation score exhibited a survival time that was considerably longer in contrast with those in the group with a low-RNA methylation score. The capacity of RS to predict whether or not immunotherapy would be beneficial was explored further. In the group with a high-RNA methylation score, the objective response rate to the anti-PD-L1 therapy was substantially greater compared to that observed in the subgroup with a low-RNA methylation score. Additionally, there were variations across various RS groups in terms of clinical features, tumor mutation burden, and the infiltration level of immune cells. After binary tree analysis and PCR verification of 34 prognostic genes, it is finally found that the six genes of MAGOH3P, TRBJ2_3, YTHDF1P1, RP11_323D18.5, RP11_405M12.2, and ADAM30 are significantly overexpressed in cancer tissues. These genes can be used as potential biomarkers of endometrial cancer and provide data support for precise immunotherapy in UCEC tumors.

Identification of an immune checkpoint gene signature that accurately predicts prognosis and immunotherapy response in endometrial carcinoma.

In this study, we performed a bioinformatics analysis to identify immune checkpoint genes (ICGs) associated with prognosis and the immunotherapeutic response in endometrial carcinoma (EC) patients. We classified 47 ICGs into high, medium, and low expression groups by performing RNA-sequencing data analysis of EC patient samples from The Cancer Genome Atlas (n = 521) and GSE77688 (n = 88) datasets. Univariate Cox regression analysis showed that seven ICGs (VTCN1, TNFRSF18, TNFRSF14, TNFRSF4, CD40LG, TMIGD2, and BTLA) were associated with prognosis in EC patients. Spearman correlation analysis showed that prognosis-related ICGs correlated positively with immunotherapy response factors, including tumor mutation burden (TMB), mismatch repair gene mutations, neoantigens, clinical stages, and adaptive immune resistance pathway genes. We identified a prognostic gene signature of four ICGs (IDO1, CD274, CTLA4, and TNFRSF14) that accurately predicted survival outcomes of EC patients. TIMER database and Kaplan-Meier survival analysis showed that OS among EC patients with low TNFRSF14 expression was significantly shorter than among those with high TNFRSF14 expression. In vitro experiments showed that TNFRSF14 silencing increased the migration and invasiveness of EC cells by promoting epithelial-mesenchymal transition (EMT). Collectively, these findings reveal an immune checkpoint gene signature that accurately predicts survival outcomes and immunotherapeutic responses in EC patients.

Flurbiprofen axetil reduces postoperative sufentanil consumption and enhances postoperative analgesic effects in patients with colorectal cancer surgery.

To investigate the effects of different strategies of flurbiprofen axetil (FA) administration on postoperative pain and sufentanil (SF) consumption after open colorectal cancer (CRC) surgery. Forty patients undergoing elective CRC resection were divided into two groups (n = 20 each). Patients in the F50+50 group received 50 mg of intravenous FA 30 min before skin incision and six hours after the first dose; patients in the F100 group received 100 mg of intravenous FA 30 min before skin incision. Perioperative plasma FA (CFA) and SF concentrations (CSF) were determined. Analgesic and sedative efficacy were evaluated using the visual analogue scale (VAS), Bruggman Comfort Scale (BCS), and Ramsay sedation scale. The time to the first PCIA trigger, the number of patients that pressed the PCIA trigger within 24 h after surgery, and the cumulative doses of SF consumption within 6 and 24 h after surgery were recorded. At postoperative 6 and 24 h, CFA was significantly higher, CSF was significantly lower, and the number of patients that pressed the PCIA trigger and the consumption of SF were significantly lower in the F50+50 group compared with the F100 group. At postoperative 4 h, VAS and BCS were significantly lower in the F50+50 group compared with the F100 group (P < 0.05). An administration strategy that maintains a relatively high plasma FA concentration at 6-24 h post-operatively may reduce postoperative inflammatory pain and SF-requirement in patients undergoing CRC resection.