Osteosarcoma is a quickly developing, malignant cancer of the bone, which is associated with a bad prognosis. In osteosarcoma, hypoxia promotes the malignant phenotype, which results in a cascade of immunosuppressive processes, poor prognosis, and a high risk of metastasis. Nonetheless, additional methodologies for the study of hyperoxia in the tumor microenvironment also need more analysis. We obtained 88 children patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and 53 children patients with RNA sequence and clinicopathological data from the Gene Expression Omnibus (GEO). We developed a four-gene signature related to hypoxia to reflect the immune microenvironment in osteosarcoma that predicts survival. A high-risk score indicated a poor prognosis and immunosuppressive microenvironment. The presence of the four-gene signature related to hypoxia was correlated with clinical and molecular features and was an important prognostic predictor for pediatric osteosarcoma patients. In summary, we established and validated a four-gene signature related to hypoxia to forecast recovery and presented an independent prognostic predictor representing overall immune response strength within the osteosarcoma microenvironment.

Objective. The aim of this research was to create a new genetic signature of immune checkpoint-associated genes as a prognostic method for pediatric acute myeloid leukemia (AML). Methods. Transcriptome profiles and clinical follow-up details were obtained in Therapeutically Applicable Research to Generate Effective Treatments (TARGET), a database of pediatric tumors. Secondary data was collected from the Gene Expression Omnibus (GEO) to test the observations. In univariate Cox regression and multivariate Cox regression studies, the expression of immune checkpoint-related genes was studied. A three-mRNA signature was developed for predicting pediatric AML patient survival. Furthermore, the GEO cohort was used to confirm the reliability. A bioinformatics method was utilized to identify the diagnostic and prognostic value. Results. A three-gene (STAT1, BATF, EML4) signature was developed to identify patients into two danger categories depending on their OS. A multivariate regression study showed that the immune checkpoint-related signature (STAT1, BATF, EML4) was an independent indicator of pediatric AML. By immune cell subtypes analyses, the signature was correlated with multiple subtypes of immune cells. Conclusion. In summary, our three-gene signature can be a useful tool to predict the OS in AML patients.

Papillary renal cell carcinoma (pRCC) is one of the epithelial renal cell carcinoma (RCC) histological subtypes. Ferroptosis is a new iron-dependent form of cell death that has been seen in a variety of clinical situations. Using differentially expressed ferroptosis-related long non-coding RNAs (lncRNAs) from patients with pRCC in The Cancer Genome Atlas; we built a prognostic lncRNA-based signature. We discovered seven different lncRNAs that were strongly linked to the prognosis of patients with pRCC. High-risk scores were linked to a poor prognosis for pRCC, which was confirmed by the findings of Kaplan–Meier studies. In addition, the constructed lncRNA signature has a 1-year area under the curve (AUC) of 0.908, suggesting that it has a high predictive value in pRCC. In the high-risk group, Gene set enrichment analyses (GSEA) analysis identified immunological and tumor-related pathways. Furthermore, single-sample GSEA (ssGSEA) revealed significant differences in T cell functions checkpoint, antigen presenting cell (APC) co-stimulation, inflammation promoting, and para inflammation between the two groups with different risk scores. In addition, immune checkpoints like PDCD1LG2 (PD-L2), LAG3, and IDO1 were expressed differently in the two risk groups. In summary, a novel signature based on ferroptosis-related lncRNAs could be applied in predicting the prognosis of patients with pRCC.

Acute kidney injury (AKI) has a high mortality rate, but its pathogenesis remains unclear Lipopolysaccharide (LPS)-mediated renal tubular epithelial pyroptosis is involved in the pathogenesis of AKI. NLR family of pyrin domains containing 3 (NLRP3) plays an important role in pyroptosis. To further understand the transcriptional regulation mechanism of NLRP3, the peripheral blood of patients with AKI was analyzed in this study, showing that the levels of NLRP3 and cell pyroptosis in patients with AKI were significantly higher than those in normal controls. Furthermore, elevated levels of NLRP3 and cell pyroptosis were found in renal tubular epithelial cells after LPS treatment. Transcription factor ETS Proto-Oncogene 1 (ETS1) could bind to the upstream promoter transcription site of NLRP3 to transactivate NLRP3 in renal tubular epithelial cells. The cell pyroptosis level also decreased by knocking down ETS1. It is concluded that knocking down of ETS1 may reduce the renal tubular epithelial pyroptosis by regulating the transcription of NLRP3, thus relieving AKI. ETS1 is expected to be a molecular target for the treatment of AKI. Graphical abstract

Ferroptosis is a recently identified form of cell death that is distinct from the conventional modes such as necrosis, apoptosis, and autophagy. Its role in bronchopulmonary dysplasia (BPD) remains inadequately understood. To address this gap, we obtained BPD-related RNA-seq data and ferroptosis-related genes (FRGs) from the GEO database and FerrDb, respectively. A total of 171 BPD-related differentially expressed ferroptosis-related genes (DE-FRGs) linked to the regulation of autophagy and immune response were identified. Least absolute shrinkage and selection operator and SVM-RFE algorithms identified 23 and 14 genes, respectively, as marker genes. The intersection of these 2 sets yielded 9 genes (ALOX12B, NR1D1, LGMN, IFNA21, MEG3, AKR1C1, CA9, ABCC5, and GALNT14) with acceptable diagnostic capacity. The results of the functional enrichment analysis indicated that these identified marker genes may be involved in the pathogenesis of BPD through the regulation of immune response, cell cycle, and BPD-related pathways. Additionally, we identified 29 drugs that target 5 of the marker genes, which could have potential therapeutic implications. The ceRNA network we constructed revealed a complex regulatory network based on the marker genes, further highlighting their potential roles in BPD. Our findings offer diagnostic potential and insight into the mechanism underlying BPD. Further research is needed to assess its clinical utility.