Identification of key biomarkers related to epithelial‐mesenchymal transition and immune infiltration in ameloblastoma using integrated bioinformatics analysis

Zhang, Zhao; Ye, Peng; Dang, Jingyi; Liu, Xincheng; Zhu, Dongze; Zhang, Yushen; Shi, Yubo; Fan, Hongbin

doi:10.1111/odi.14173

Cited by 18 publications

(15 citation statements)

References 65 publications

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“…According to Santos et al [68] and the present study, CDK1 was considered a critical gene, playing a significant role in the etiology of ameloblastoma. Zhang et al [71] recently executed an integrated bioinformatics analysis to demonstrate potential biomarkers and molecular mechanisms associated with the epithelialmesenchymal transition (EMT) and immune infiltration in ameloblastoma.…”

Section: Discussionmentioning

confidence: 99%

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Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

Bayat

Mirzaeian

Taherkhani

2022

International Journal of Dentistry

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Objective. Ameloblastoma is a benign odontogenic tumor that may lead to ameloblastic carcinoma. is study aimed to determine potential signaling pathways and biological processes, critical genes and their regulating transcription factors (TFs), and miRNAs, as well as protein kinases involved in the etiology of primary ameloblastoma. Methods. e dataset GSE132472 was obtained from the GEO database, and multivariate statistical analyses were applied to identify di erentially expressed genes (DEGs) in primary ameloblastoma tissues compared to the corresponding normal gingiva samples. A protein-protein interaction (PPI) map was built using the STRING database. e Cytoscape software identi ed signi cant modules and the hub genes within the PPI network. Gene Ontology annotation and signaling pathway analyses were executed by employing the DAVID and Reactome databases, respectively. Signi cant TFs and miRNAs acting on the hub genes were identi ed using the iRegulon plugin and MiRWalk 2.0 database, respectively. A protein kinase enrichment analysis was conducted using the online Kinase Enrichment Analysis 2 (KEA2) web server. e approved drugs acting on the hub genes were also found. Results. A total of 1,629 genes were di erentially expressed in primary ameloblastoma (P value <0.01 and |Log2FC| > 1). HRAS, CDK1, MAPK3, ERBB2, COL1A1, CYCS, and BRCA1 demonstrated high degree and betweenness centralities in the PPI network. E2F4 was the most signi cant TF acting on the hub genes. BTK was the protein kinase signi cantly enriched by the TFs. Cholesterol biosynthesis was considerably involved in primary ameloblastoma. Conclusions. is study provides an intuition into the potential mechanisms involved in the etiology of ameloblastoma.

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Section: Discussionmentioning

confidence: 99%

“…e authors used the CIBERSORT algorithm to study the immune infiltration in ameloblastoma. Zhang et al [71] reported that a total of 776 genes were deregulated in ameloblastoma, in which FN1 was upregulated and was linked to the macrophage M2 polarization. e current study had certain limitations.…”

Section: Discussionmentioning

confidence: 99%

Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

Bayat

Mirzaeian

Taherkhani

2022

International Journal of Dentistry

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“…In the conservative approach, enucleation is included, and in the radical approach, excision and local reconstruction are considered. Its recurrence is a common complication of conservative treatment; although the conservative approach maintains the integrity of the bone with its growth pattern, it is associated with a high possibility of recurrence ranging from 55–90% [ 19 , 28 , 29 , 30 , 31 ]. To reduce these recurrences, complete bone resection with a safety margin has been considered an adequate option, mainly through marginal or segmental osteotomy for the mandible and partial or total maxillectomy for the maxilla.…”

Section: Discussionmentioning

confidence: 99%

“…The bioinformatics methods on microarray profile datasets represents an important opportunity and strategy to correlate the clinical and molecular features with the possible application of therapeutic and/or prognostic biomarkers of ameloblastoma. Through these assays, the existence of differential changes in inflammatory and immunological mechanisms, MAP kinases, and cell cycle deregulations in ameloblastoma has been determined [ 16 , 17 , 18 , 19 ]. As we mentioned above, with this large amount of information, it is possible to postulate candidates for new therapeutic alternatives, as well as to establish correlations with clinical and histological variables of this odontogenic tumor.…”

Section: Introductionmentioning

confidence: 99%

Conventional Ameloblastoma. A Case Report with Microarray and Bioinformatic Analysis

et al. 2022

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Ameloblastoma is a rare benign epithelial odontogenic neoplasm, but with great clinical implications, as despite its benignity and slow growth, most cases are locally aggressive with a significant recurrence rate. Histological, cellular, or molecular analyses of its pathogenesis have confirmed the complexity of this neoplasm. We present the case of a 20-year-old patient with a suggestive clinical and radiographic diagnosis of ameloblastoma. An incisional biopsy was obtained confirming the diagnosis of conventional ameloblastoma. Left hemimandibulectomy and plate reconstruction were performed. Histopathological analysis of the surgical specimen confirmed the conventional ameloblastoma with a plexiform pattern and significant areas of cystic degeneration and amyloid-like-like deposits. Additionally, a microarray was carried out with bioinformatic analysis for the enrichment, protein interaction, and determination of eight hub genes (CRP, BCHE, APP, AKT1, AGT, ACTC1, ADAM10, and APOA2) related to their pathogenesis.

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“…Recently, as high-throughput sequencing has evolved, stratifying tumor patients by bioinformatics and machine learning approaches to explore new biomarkers has proven to be reliable and useful ( Zhang et al, 2022a ; Zhang et al, 2022b ; Sun et al, 2022 ). In the current study, we first screened differential expression ofLRGs (DE-LRGs) between EWS and normal tissues.…”

Section: Introductionmentioning

confidence: 99%

Expression of lactate-related signatures correlates with immunosuppressive microenvironment and prognostic prediction in ewing sarcoma

et al. 2022

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Objectives: Ewing sarcoma (EWS) is an aggressive tumor of bone and soft tissue. Growing evidence indicated lactate as a pivotal mediator of crosstalk between tumor energy metabolism and microenvironmental regulation. However, the contribution of lactate-related genes (LRGs) in EWS is still unclear.Methods: We obtained the transcriptional data of EWS patients from the GEO database and identified differentially expressed-LRGs (DE-LRGs) between EWS patient samples and normal tissues. Unsupervised cluster analysis was utilized to recognize lactate modulation patterns based on the expression profile of DE-LRGs. Functional enrichment including GSEA and GSVA analysis was conducted to identify molecular signaling enriched in different subtypes. ESTIMATE, MCP and CIBERSORT algorithm was used to explore tumor immune microenvironment (TIME) between subtypes with different lactate modulation patterns. Then, lactate prognostic risk signature was built via univariate, LASSO and multivariate Cox analysis. Finally, we performed qPCR analysis to validate candidate gene expression.Result: A total of 35 DE-LRGs were identified and functional enrichment analysis indicated that these LRGs were involved in mitochondrial function. Unsupervised cluster analysis divided EWS patients into two lactate modulation patterns and we revealed that patients with Cluster 1 pattern were linked to poor prognosis and high lactate secretion status. Moreover, TIME analysis indicated that the abundance of multiple immune infiltrating cells were dramatically elevated in Cluster 1 to Cluster 2, including CAFs, endothelial cells, Macrophages M2, etc., which might contribute to immunosuppressive microenvironment. We also noticed that expression of several immune checkpoint proteins were clearly increased in Cluster 1 to Cluster 2. Subsequently, seven genes were screened to construct LRGs prognostic signature and the performance of the resulting signature was validated in the validation cohort. Furthermore, a nomogram integrating LRGs signature and clinical characteristics was developed to predict effectively the 4, 6, and 8-year prognosis of EWS patients.Conclusion: Our study revealed the role of LRGs in immunosuppressive microenvironment and predicting prognosis in EWS and provided a robust tool to predict the prognosis of EWS patients.

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Identification of key biomarkers related to epithelial‐mesenchymal transition and immune infiltration in ameloblastoma using integrated bioinformatics analysis

Abstract: Jackson et al., 1996). The main clinical manifestation is a progressive, painless enlargement of the jawbone, which is often diagnosed as a large tumor with cortical perforation and soft tissue invasion (Fregnani et al., 2010). Currently, surgical excision is a

Cited by 18 publications

References 65 publications

Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

Conventional Ameloblastoma. A Case Report with Microarray and Bioinformatic Analysis

Expression of lactate-related signatures correlates with immunosuppressive microenvironment and prognostic prediction in ewing sarcoma

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