Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature.
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.
['Jovanovic|Ivan|I|0000-0001-7932-9463', 'Zivkovic|Maja|M|', 'Djuric|Tamara|T|', 'Stojkovic|Ljiljana|L|', 'Jesic|Snezana|S|', 'Stankovic|Aleksandra|A|']
D018424:Cholesteatoma, Middle Ear D002908:Chronic Disease D006097:Granulation Tissue D006801:Humans D010033:Otitis Media D012189:Retrospective Studies D059467:Transcriptome
granulation tissue Cholesteatoma perimatrix microarray bioinformatic gene expression