Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

Identification of feature genes and key biological pathways in immune-mediated necrotizing myopathy: High-throughput sequencing and bioinformatics analysis.

Background: Immune-mediated necrotizing myopathy (IMNM), a subgroup of idiopathic inflammatory myopathies (IIMs), is characterized by severe proximal muscle weakness and prominent necrotic fibers but no infiltration of inflammatory cells. IMNM pathogenesis is unclear. This study investigated key biomarkers and potential pathways for IMNM using high-throughput sequencing and bioinformatics technology. Methods: RNA sequencing was conducted in 18 IMNM patients and 10 controls. A combination of weighted gene coexpression network analysis (WGCNA) and differentially expressed gene (DEG) analysis was conducted to identify IMNM-related DEGs. Feature genes were screened out by employing the protein-protein interaction (PPI) network, support vector machine-recursive feature elimination (SVM-RFE), and least absolute shrinkage selection operator (LASSO). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify their differential expression, and the receiver operating characteristic curve (ROC) was used to evaluate their diagnostic efficiency. Functional enrichment analysis was applied to reveal the hidden functions of feature genes. Furthermore, 28 immune cell abundance patterns in IMNM samples were measured. Results: We identified 193 IMNM-related DEGs that were aberrantly upregulated in the IMNM population and were closely associated with immune-inflammatory responses, regulation of skeletal and cardiac muscle contraction, and lipoprotein metabolism. With the help of the PPI network and the LASSO and SVM-RFE algorithms, three feature genes, LTK, MYBPH, and MYL4, were identified and further confirmed by qRT-PCR. ROC curves among IMNM, dermatomyositis (DM), inclusion body myositis (IBM), and polymyositis (PM) samples validated the LTK and MYL4 genes as IMNM-specific feature markers. In addition, all three genes had a notable association with the autophagy-lysosome pathway and immune-inflammatory responses. Ultimately, IMNM displayed a marked immune-cell infiltrative microenvironment. The most significant correlation was found between CD4 T cells, CD8 T cells, macrophages, natural killer (NK) cells, and dendritic cells (DCs). Conclusions: LTK, MYBPH, and MYL4 were identified as potential key molecules for IMNM and are believed to play a role in the autophagy-lysosome pathway and muscle inflammation.

Potential common molecular mechanisms between Sjögren syndrome and inclusion body myositis: a bioinformatic analysis and in vivo validation.

Background: Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy that typically affects the quadriceps and finger flexors. Sjögren's syndrome (SS), an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands has been reported to share common genetic and autoimmune pathways with IBM. However, the exact mechanism underlying their commonality remains unclear. In this study, we investigated the common pathological mechanisms involved in both SS and IBM using a bioinformatic approach. Methods: IBM and SS gene expression profiles were obtained from the Gene Expression Omnibus (GEO). SS and IBM coexpression modules were identified using weighted gene coexpression network analysis (WGCNA), and differentially expressed gene (DEG) analysis was applied to identify their shared DEGs. The hidden biological pathways were revealed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, protein-protein interaction (PPI) networks, cluster analyses, and hub shared gene identification were conducted. The expression of hub genes was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). We then analyzed immune cell abundance patterns in SS and IBM using single-sample gene set enrichment analysis (ssGSEA) and investigated their association with hub genes. Finally, NetworkAnalyst was used to construct a common transcription factor (TF)-gene network. Results: Using WGCNA, we found that 172 intersecting genes were closely related to viral infection and antigen processing/presentation. Based on DEG analysis, 29 shared genes were found to be upregulated and enriched in similar biological pathways. By intersecting the top 20 potential hub genes from the WGCNA and DEG sets, three shared hub genes (PSMB9, CD74, and HLA-F) were derived and validated to be active transcripts, which all exhibited diagnostic values for SS and IBM. Furthermore, ssGSEA showed similar infiltration profiles in IBM and SS, and the hub genes were positively correlated with the abundance of immune cells. Ultimately, two TFs (HDGF and WRNIP1) were identified as possible key TFs. Conclusion: Our study identified that IBM shares common immunologic and transcriptional pathways with SS, such as viral infection and antigen processing/presentation. Furthermore, both IBM and SS have almost identical immune infiltration microenvironments, indicating similar immune responses may contribute to their association.

Head and neck carcinoma in children: A clinicopathological study of 42 cases.

Background/purpose: Cancer is an important part of the global burden of childhood diseases. Head and neck carcinoma in children is rare and related research is limited. This study aimed to investigate the clinicopathological features of childhood head and neck carcinoma. Materials and methods: Forty-two cases of childhood head and neck carcinoma treated in our institution were reviewed and analyzed. Results: Median age overall was 11 years. Twenty-three patients (54.8%) were male and 19 (45.2%) were female. Parotid gland location was most common (54.8%). Mucoepidermoid carcinoma and squamous cell carcinoma were the most common histological types (57.1% and 11.9%, respectively). Two patients had a history of bone marrow transplantation and two had a history of odontogenic keratocyst. The recurrence rate after treatment was 8.6%. Conclusion: Early diagnosis and treatment and close follow-up of childhood head and neck carcinoma are warranted to prevent recurrence and improve clinical outcome.

Key biomarkers and latent pathways of dysferlinopathy: Bioinformatics analysis and in vivo validation.

Background: Dysferlinopathy refers to a group of muscle diseases with progressive muscle weakness and atrophy caused by pathogenic mutations of the DYSF gene. The pathogenesis remains unknown, and currently no specific treatment is available to alter the disease progression. This research aims to investigate important biomarkers and their latent biological pathways participating in dysferlinopathy and reveal the association with immune cell infiltration. Methods: GSE3307 and GSE109178 were obtained from the Gene Expression Omnibus (GEO) database. Based on weighted gene co-expression network analysis (WGCNA) and differential expression analysis, coupled with least absolute shrinkage and selection operator (LASSO), the key genes for dysferlinopathy were identified. Functional enrichment analysis Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to disclose the hidden biological pathways. Following that, the key genes were approved for diagnostic accuracy of dysferlinopathy based on another dataset GSE109178, and quantitative real-time polymerase chain reaction (qRT-PCR) were executed to confirm their expression. Furthermore, the 28 immune cell abundance patterns in dysferlinopathy were determined with single-sample GSEA (ssGSEA). Results: 1,579 differentially expressed genes (DEGs) were screened out. Based on WGCNA, three co-expression modules were obtained, with the MEskyblue module most strongly correlated with dysferlinopathy. 44 intersecting genes were recognized from the DEGs and the MEskyblue module. The six key genes MVP, GRN, ERP29, RNF128, NFYB and KPNA3 were discovered through LASSO analysis and experimentally verified later. In a receiver operating characteristic analysis (ROC) curve, the six hub genes were shown to be highly valuable for diagnostic purposes. Furthermore, functional enrichment analysis highlighted that these genes were enriched mainly along the ubiquitin-proteasome pathway (UPP). Ultimately, ssGSEA showed a significant immune-cell infiltrative microenvironment in dysferlinopathy patients, especially T cell, macrophage, and activated dendritic cell (DC). Conclusion: Six key genes are identified in dysferlinopathy with a bioinformatic approach used for the first time. The key genes are believed to be involved in protein degradation pathways and the activation of muscular inflammation. And several immune cells, such as T cell, macrophage and DC, are considered to be implicated in the progression of dysferlinopathy.

miR-762 Promotes Malignant Development of Head and Neck Squamous Cell Carcinoma by Targeting PHLPP2 and FOXO4.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is among the most common malignant tumors worldwide. This study, investigated the role of microRNA (miR)-762 in regulating HNSCC progression. MATERIALS AND METHODS: The expression levels of miR-762 in HNSCC tissues were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Statistical analyses were performed to investigate the association of miR-762 with clinicopathological features in patients with HNSCC. Cell proliferation and migration were examined by cell counting (CCK-8) and IncuCyte assays. Target genes of miR-762 were screened using bioinformatics tools and microarrays, and confirmed using a luciferase activity reporter assay, qRT-PCR and Western blot analysis. Recuse experiments were performed to detect whether target genes mediated the effects of miR-762 on HNSCC cells. The in vivo effects of miR-762 were verified using tumor xenografts. RESULTS: HNSCC clinical specimens showed high expression levels of miR-762, which positively correlated with tumor-node-metastasis (TNM) stage and poor prognosis of HNSCC. miR-762 overexpression promoted the proliferation and migration of HNSCC cells in vitro. In addition, overexpression of miR-762 upregulated the expression of phosphorylated AKT (p-AKT) and mesenchymal markers (N-cadherin and vimentin), but suppressed epithelial marker (E-cadherin) expression. miR-762 also promoted HNSCC tumor growth in vivo. PH domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) and Forkhead box O4 (FOXO4) were direct target genes of miR-762. HNSCC tissues had low expression levels of PHLPP2 and FOXO4, showing a negative correlation with miR-762 expression. Moreover, silencing of PHLPP2 and FOXO4 mimicked the tumor-promotive effects of miR-762 on HNSCC cells. Notably, overexpression of PHLPP2 and FOXO4 abolished the pro-tumoral function of miR-762 on cell proliferation and migration. CONCLUSION: miR-762 promotes HNSCC progression by targeting PHLPP2 and FOXO4. Therefore, miR-762 might be a potential diagnostic or therapeutic target for HNSCC.

Clinicopathologic Analysis of Oral Squamous Cell Carcinoma After 125I Interstitial Brachytherapy.

Oral squamous cell carcinoma is a common malignancy in the head and neck region. Brachytherapy after radical surgery has achieved much progress as a cancer adjuvant treatment. This study focused on the pathologic characteristics of the patients with oral squamous cell carcinoma who underwent seed implantation after radical surgery, and the relationship of these characteristics with prognosis. Thus, 76 patients with oral squamous cell carcinoma, who were treated with surgery and subsequently with iodine 125 (125I) radioactive seed implantation, were recruited in this study. We summarized the demographic information, tumor size, location, clinical stage, prognosis, and pathologic characteristics, and discussed the correlations between prognosis and histologic features of oral squamous cell carcinoma after seed implantation. The data showed that the median age was 64 years old, the male/female ratio was 47/29, and the frequent location of the carcinoma was the tongue (35.5%). The median follow-up time was 126 months, and of the patients, 52 (68.4%) exhibited recurrent tumors. The 5-year survival rate was 81.5%, and the local control rate in 6 months was 95.3%. Microscopically, 25 cases demonstrated lymph node metastasis, there was obvious necrosis in 13 cases, and 55 cases exhibited confirmed adjacent tissue invasion including muscle, gland, vessel, nerve, and bone infiltration. Among those, vascular infiltration (13 cases) was significantly correlated with tumor recurrence ( P < .05). This study suggests that detailed pathologic diagnosis and microscopic description, especially of vascular infiltration, was valuable in the prognosis prediction of brachytherapy.