Differential Gene Expression in Cholesteatoma by DNA Chip Analysis

Macias, John D.; Gerkin, Richard; Locke, Darren; Macias, MiMi P.

doi:10.1002/lary.24176

Cited by 21 publications

(27 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, recently performed comprehensive genetic studies on differently expressed genes on cholesteatoma in comparison to the skin provided a genetic map for various cholesteatoma related transcripts including up and down-regulated genes. Through this knowledge, targeting drug therapy might be accessed in the future [139,140]. …”

Section: Is There Any Trial For Non-surgical Treatment? ‘Future Prospmentioning

confidence: 99%

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives

Hamed

Nakata

Sayed

et al. 2016

Clin Exp Otorhinolaryngol

View full text Add to dashboard Cite

Cholesteatoma is a cystic non tumorous lesion of the temporal bone that has the ability to destroy nearby structures by its power to cause bone resorption and as a result, fatal complications prevail. We aimed to conduct a comprehensive review for pathogenesis of acquired cholesteatoma, bone resorption mechanisms, and offer a future vision of this serious disease. We have reviewed different theories for pathogenesis of acquired cholesteatoma including the most relevant and updated ones with special emphasis on the mechanisms of bone resorption through Medline/PubMed research using the keywords ‘aetiopathogenesis, bone resorption, acquired cholesteatoma, temporal bone, and cytokines.’ In order to strengthen our study, we searched the reference lists of identified reviews. Cholesteatoma is a subject of debate among otolaryngologists since it was prescribed firstly. Over many decades, several theories were postulated for aetiopathogenesis of cholesteatoma with a tendency to follow more than one theory to explain the proper nature of that disease. Until now, the mechanism of bone resorption has yet to be more clarified. In the last century, a leap has occurred in the field of biomolecular cholesteatoma research which improved our knowledge about its pathophysiology and bone destructive mechanism. However, surgery is still the only available treatment. We conclude that discovery of new therapeutic choices for cholesteatoma other than surgery by the use of anti-growth, anti-proliferative, apoptotic agents as well as medications that antagonize osteoclastogenesis should be the main concern in the future clinical and experimental research work. Also, searching for predictors of the aggressiveness of cholesteatoma can affect the timing of intervention and prevent occurrence of complications.

show abstract

Section: Is There Any Trial For Non-surgical Treatment? ‘Future Prospmentioning

confidence: 99%

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives

Hamed

Nakata

Sayed

et al. 2016

Clin Exp Otorhinolaryngol

View full text Add to dashboard Cite

show abstract

“…Three clades of serpins were represented by DEGs in the process, SERPINA3 from inflammatory response associated clade A, SERPINB3 , SERPINB4 , and SERPINB7 from cytotoxic and apoptotic proteases prevention clade B, and SERPINE2 from clade E, which contains the inhibitors of thrombin, uPA, tPA, and plasmin . The expression of different forms of serpins have also been identified previously in the cholesteatoma . The effects of downregulated endopeptidase inhibitors in the cholesteatoma perimatrix compared to COM without cholesteatoma should be further investigated.…”

Section: Discussionmentioning

confidence: 76%

“…The current study's approach offers an overall look at molecular mechanisms that describe the cholesteatoma entity by focusing exclusively on the perimatrix processes in comparison to COM granulation tissue. In previous high‐throughput gene‐expression studies, the comparison of cholesteatoma tissue with the external auditory canal or retroauricular skin has become a standard model for investigating dysregulated molecular mechanisms in cholesteatoma . However, this type of study is limited and does not give us the answer regarding the perimatrix‐specific molecular processes, which could be related to abnormal behaviour of the cholesteatoma phenotype.…”

Section: Resultsmentioning

confidence: 99%

“…38 The expression of different forms of serpins have also been identified previously in the cholesteatoma. [39][40][41] The effects of downregulated endopeptidase inhibitors in the cholesteatoma perimatrix compared to COM without cholesteatoma should be further investigated. For example, higher levels of serpin B3 were detected in successful healing that can differentiate between pathogenic and nonpathogenic burn healing in diabetic mice.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature

et al. 2019

View full text Add to dashboard Cite

Objectives/Hypothesis To establish comprehensive transcriptomic profiles of cholesteatoma perimatrix tissue and granulation tissue from chronic otitis media (COM) that did not develop cholesteatoma, which can indicate molecular pathways involved in the cholesteatoma perimatrix pathology and invasiveness. Study Design Retrospective Case Series. Methods Transcriptome data were obtained from cholesteatoma perimatrix tissue and COM granulation tissue by an Illumina iScan microarray. Differentially expressed genes (DEGs) were subsequently analyzed using both bioinformatical functional annotation and network analysis. Expression of candidate genes (MMP9 and LCN2) was validated by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) on a larger group of samples. Results Analysis of the transcriptome led to the identification of 169 differentially expressed genes between investigated tissues. Bioinformatic analysis suggested that most significant biological processes involving DEGs were previously described in cholesteatoma pathology. Network analysis identified ERBB2, TFAP2A, and TP63 as major hubs of the DEGs molecular network. Furthermore, it was observed that the cellular component most significantly enriched in DEGs was extracellular space containing 47 DEGs. Using qRT‐PCR, it was confirmed that mRNA levels of the major extracellular hub (MMP9) are increased, whereas its interacting molecule (LCN2) mRNA levels were decreased in cholesteatoma perimatrix tissue compared to COM granulation tissue. Conclusions The current study approach offers an overall look at molecular mechanisms that describe the cholesteatoma entity by focusing exclusively on the perimatrix processes in comparison to COM granulation tissue. The observed differences in gene expression between cholesteatoma perimatrix and COM granulation tissue could suggest novel markers potentially influenced by the perimatrix–matrix molecular interplay, which is not present in COM without cholesteatoma. Level of Evidence NA Laryngoscope, 130:E220–E227, 2020

show abstract

“…There are two published large‐scale analyses comparing RNA transcript expression in cholesteatoma to that in skin of the external auditory canal. These have shown several hundred genes are differentially regulated in cholesteatoma samples, including genes with products involved in growth, differentiation, signal transduction, cell communication, protein metabolism and cytoskeleton formation . However, the results from these studies are inconsistent, and are measuring gene expression once cholesteatoma has formed, and so have failed to significantly further our understanding of constitutional risk.…”

Section: Introductionmentioning

confidence: 99%

The genetics of cholesteatoma. A systematic review using narrative synthesis

Jennings

Prinsley

Philpott

et al. 2017

Clinical Otolaryngology

View full text Add to dashboard Cite

Objective: A cholesteatoma is a mass of keratinising epithelium in the middle ear. It is a rare disorder that is associated with significant morbidity, and its causative risk factors are poorly understood; on a global scale, up to a million people are affected by this each year. We have conducted a systematic literature review to identify reports about the heritability of cholesteatoma or any constitutional genetic factors that may be associated with its aetiology.Data Sources: A systematic search of MEDLINE (EBSCO) and two databases of curated genetic research (OMIM and Phenopedia) was conducted.Study Selection: The participants and populations of interest for this review were people treated for cholesteatoma and their family members. The studies of interest reported evidence of heritability for the trait, or any association with congenital syndromes and particular genetic variants.Data Extraction: The searches identified 449 unique studies, of which 35 were included in the final narrative synthesis.Data Synthesis: A narrative synthesis was conducted, and data were tabulated to record characteristics, including study design, genetic data and author conclusions.Most of the studies identified in the literature search, and described here, are case reports and so represent the lowest level of evidence. In a few case reports, congenital and acquired cholesteatomas have been shown to segregate within families in the pattern typical of a monogenic or oligogenic disorder with incomplete penetrance. Evidence from syndromic cases could suggest that genes controlling ear morphology may be risk factors for cholesteatoma formation.Conclusions: This is the first systematic review about the genetics of cholesteatoma, and we have identified a small body of relevant literature that provides evidence of a heritable component for its aetiology. Cholesteatoma is a complex and heterogeneous clinical phenotype, and it is often associated with chronic otitis media and with some rare congenital syndromes known to affect ear morphology and related pathologies.

show abstract

Differential Gene Expression in Cholesteatoma by DNA Chip Analysis

Abstract: We present a comprehensive, human genome-wide survey of disease-associated gene expression that extends the public database and provides new evidence for molecular mechanisms involved in cholesteatoma pathology. Laryngoscope, 123:S1-S21, 2013.

Cited by 21 publications

References 39 publications

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives

Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature

The genetics of cholesteatoma. A systematic review using narrative synthesis

Contact Info

Product

Resources

About