Identification of important genes related to anoikis in acute myocardial infarction.

Acute myocardial infarction (AMI) increasingly precipitates severe heart failure, with diagnoses now extending to progressively younger demographics. The focus of this study was to pinpoint critical genes linked to both AMI and anoikis, thereby unveiling potential novel biomarkers for AMI detection and intervention. Differential analysis was performed to identify significant differences in expression, and gene functionality was explored. Weighted gene coexpression network analysis (WGCNA) was used to construct gene coexpression networks. Immunoinfiltration analysis quantified immune cell abundance. Protein-protein interaction (PPI) analysis identified the proteins that interact with theanoikis. MCODE identified key functional modules. Drug enrichment analysis identified relevant compounds explored in the DsigDB. Through WGCNA, 13 key genes associated with anoikis and differentially expressed genes were identified. GO and KEGG pathway enrichment revealed the regulation of apoptotic signalling pathways and negative regulation of anoikis. PPI network analysis was also conducted, and 10 hub genes, such as IL1B, ZAP70, LCK, FASLG, CD4, LRP1, CDH2, MERTK, APOE and VTN were identified. IL1B were correlated with macrophages, mast cells, neutrophils and Tcells in MI, and the most common predicted medications were roxithromycin, NSC267099 and alsterpaullone. This study identified key genes associated with AMI and anoikis, highlighting their role in immune infiltration, diagnosis and medication prediction. These findings provide valuable insights into potential biomarkers and therapeutic targets for AMI.

A Machine Learning-Based Classification of Immunogenic Cell Death Regulators and Characterisation of Immune Microenvironment in Acute Ischemic Stroke.

Immunogenic cell death (ICD) regulators exert a crucial part in quite a few in numerous biological processes. This study aimed to determine the function and diagnostic value of ICD regulators in acute ischemic stroke (AIS). 31 significant ICD regulators were identified from the gene expression omnibus (GEO) database in this work (the combination of the GSE16561 dataset and the GSE37587 dataset in the comparison of non-AIS and AIS patients). The random forest model was applied and 15 potential ICD regulators were screened to forecast the probability of AIS. A nomogram, on the basis of 11 latent ICD regulators, was performed. The resolution curve analysis indicated that patients can gain benefits from the nomogram. The consensus clustering approach was applied, and AIS patients were divided into 2 ICD clusters (cluster A and cluster B) based on the identified key ICD regulatory factors. To quantify the ICD pattern, 181 ICD-related dissimilarly expressed genes (DEGs) were selected for further investigation. The expression levels of NFKB1, NFKB2, and PARP1 were greater in gene cluster A than in gene cluster B. In conclusion, ICD regulators exerted a crucial part in the progress of AIS. The investigation made by us on ICD patterns perhaps informs prospective immunotherapeutic methods for AIS.

HOXC6 impacts epithelial-mesenchymal transition and the immune microenvironment through gene transcription in gliomas.

BACKGROUND: Gliomas are the most common primary malignant tumours of the central nervous system (CNS). To improve the prognosis of glioma, it is necessary to identify molecular markers that may be useful for glioma therapy. HOXC6, an important transcription factor, is involved in multiple cancers. However, the role of HOXC6 in gliomas is not clear. METHODS: Bioinformatic and IHC analyses of collected samples (n = 299) were performed to detect HOXC6 expression and the correlation between HOXC6 expression and clinicopathological features of gliomas. We collected clinical information from 177 to 299 patient samples and estimated the prognostic value of HOXC6. Moreover, cell proliferation assays were performed. We performed Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) based on ChIP-seq and public datasets to explore the biological characteristics of HOXC6 in gliomas. RNA-seq was conducted to verify the relationship between HOXC6 expression levels and epithelial-mesenchymal transition (EMT) biomarkers. Furthermore, the tumour purity, stromal and immune scores were evaluated. The relationship between HOXC6 expression and infiltrating immune cell populations and immune checkpoint proteins was also researched. RESULTS: HOXC6 was overexpressed and related to the clinicopathological features of gliomas. In addition, knockdown of HOXC6 inhibited the proliferation of glioma cells. Furthermore, increased HOXC6 expression was associated with clinical progression. The biological role of HOXC6 in gliomas was primarily associated with EMT and the immune microenvironment in gliomas. High HOXC6 expression was related to high infiltration by immune cells, a low tumour purity score, a high stromal score, a high immune score and the expression of a variety of immune checkpoint genes, including PD-L1, B7-H3 and CLTA-4. CONCLUSIONS: These results indicated that HOXC6 might be a key factor in promoting tumorigenesis and glioma progression by regulating the EMT signalling pathway and might represent a novel immune therapeutic target in gliomas.

Noncoding RNAs involved in the STAT3 pathway in glioma.

Glioma is the most common malignant primary brain tumour in adults. Despite improvements in neurosurgery and radiotherapy, the prognosis of glioma patients remains poor. One of the main limitations is that there are no proper clinical therapeutic targets for glioma. Therefore, it is crucial to find one or more effective targets. Signal transducer and activator of transcription 3 (STAT3) is a member of the STAT family of genes. Abnormal expression of STAT3 is involved in the process of cell proliferation, migration, invasion, immunosuppression, angiogenesis, dryness maintenance, and resistance to radiotherapy and chemotherapy in glioma. Therefore, STAT3 has been considered an ideal therapeutic target in glioma. Noncoding RNAs (ncRNAs) are a group of genes with limited or no protein-coding capacity that can regulate gene expression at the epigenetic, transcriptional and posttranscriptional level. In this review, we summarized the ncRNAs that are correlated with the ectopic expression of STAT3 in glioma.

The expression and prognostic value of the epidermal growth factor receptor family in glioma.

BACKGROUND: The epidermal growth factor receptor (EGFR) family belongs to the transmembrane protein receptor of the tyrosine kinase I subfamily and has 4 members: EGFR/ERBB1, ERBB2, ERBB3, and ERBB4. The EGFR family is closely related to the occurrence and development of a variety of cancers. MATERIALS/METHODS: In this study, we used multiple online bioinformatics websites, including ONCOMINE, TCGA, CGGA, TIMER, cBioPortal, GeneMANIA and DAVID, to study the expression profiles, prognostic values and immune infiltration correlations of the EGFR family in glioma. RESULTS: We found that EGFR and ERBB2 mRNA expression levels were higher in glioblastoma (GBM, WHO IV) than in other grades (WHO grade II & III), while the ERBB3 and ERBB4 mRNA expression levels were the opposite. EGFR and ERBB2 were notably downregulated in IDH mutant gliomas, while ERBB3 and ERBB4 were upregulated, which was associated with a poor prognosis. In addition, correlation analysis between EGFR family expression levels and immune infiltrating levels in glioma showed that EGFR family expression and immune infiltrating levels were significantly correlated. The PPI network of the EGFR family in glioma and enrichment analysis showed that the EGFR family and its interactors mainly participated in the regulation of cell motility, involving integrin receptors and Rho family GTPases. CONCLUSIONS: In summary, the results of this study indicate that the EGFR family members may become potential therapeutic targets and new prognostic markers for glioma.

MicroRNAs involved in the EGFR pathway in glioblastoma.

Glioblastoma (GBM) is the most common primary malignant tumor in adults, and its morbidity and mortality are very high. Although progress has been achieved in the treatment of GBM, such as surgery, chemotherapy and radiotherapy, in recent years, the prognosis of patients with GBM has not improved significantly. MicroRNAs (miRNAs) are endogenous noncoding single-stranded RNAs consisting of approximately 20-22 nucleotides that regulate gene expression at the posttranscriptional level by binding to target protein-encoding mRNAs. Notably, miRNAs regulate various carcinogenic pathways, one of which is the epidermal growth factor receptor (EGFR) signaling pathway, which controls cell proliferation, invasion, migration, angiogenesis and apoptosis. In this review, we summarize the novel discoveries of roles for miRNAs targeting the factors in the EGFR signaling pathway in the occurrence and development of GBM. In addition, we describe their potential roles as biomarkers for the diagnosis and prognosis of GBM and for determining the treatment resistance of GBM and the efficacy of therapeutic drugs.