Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature
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2020
Authors
Jovanović, Ivan G.Živković, Maja
Đurić, Tamara
Stojković, Ljiljana S.
Ješić, Snežana
Stanković, Aleksandra
Article (Published version)
,
© 2019 The American Laryngological, Rhinological and Otological Society, Inc
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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 invo...lving 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. © 2019 The American Laryngological, Rhinological and Otological Society, Inc.
Keywords:
Cholesteatoma perimatrix / granulation tissue / microarray / bioinformatic / gene expressionSource:
The Laryngoscope, 2020, 130, 4, E220-E227Funding / projects:
- Genetic basis of human vascular and inflammatory diseases (RS-MESTD-Basic Research (BR or ON)-175085)
DOI: 10.1002/lary.28084
ISSN: 0023-852X
PubMed: 31132150
WoS: 000521124400016
Scopus: 2-s2.0-85076835363
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VinčaTY - JOUR AU - Jovanović, Ivan G. AU - Živković, Maja AU - Đurić, Tamara AU - Stojković, Ljiljana S. AU - Ješić, Snežana AU - Stanković, Aleksandra PY - 2020 UR - https://vinar.vin.bg.ac.rs/handle/123456789/8684 AB - 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. © 2019 The American Laryngological, Rhinological and Otological Society, Inc. T2 - The Laryngoscope T1 - Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature VL - 130 IS - 4 SP - E220 EP - E227 DO - 10.1002/lary.28084 ER -
@article{ author = "Jovanović, Ivan G. and Živković, Maja and Đurić, Tamara and Stojković, Ljiljana S. and Ješić, Snežana and Stanković, Aleksandra", year = "2020", abstract = "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. © 2019 The American Laryngological, Rhinological and Otological Society, Inc.", journal = "The Laryngoscope", title = "Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature", volume = "130", number = "4", pages = "E220-E227", doi = "10.1002/lary.28084" }
Jovanović, I. G., Živković, M., Đurić, T., Stojković, L. S., Ješić, S.,& Stanković, A.. (2020). Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature. in The Laryngoscope, 130(4), E220-E227. https://doi.org/10.1002/lary.28084
Jovanović IG, Živković M, Đurić T, Stojković LS, Ješić S, Stanković A. Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature. in The Laryngoscope. 2020;130(4):E220-E227. doi:10.1002/lary.28084 .
Jovanović, Ivan G., Živković, Maja, Đurić, Tamara, Stojković, Ljiljana S., Ješić, Snežana, Stanković, Aleksandra, "Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature" in The Laryngoscope, 130, no. 4 (2020):E220-E227, https://doi.org/10.1002/lary.28084 . .