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ISMICS 2023 Annual Meeting
31 May - 3 June, 2023 | Boston, MA
D60
Uncovering The Molecular Pathways In Iatrogenic Tracheal Stenosis: One Step Closer To Personalized Medicine
Poster Presenter
Authors
Affiliations
Part of Topic
Thoracic Surgery
Uncovering the Molecular Pathways in Iatrogenic Tracheal Stenosis:
One Step Closer to Molecular Medicine
Russell Seth Martins, Joanna Weber, Kostantinos Poulikidis, Al Haitham Al Shetawi, Robert S. Lebovics, Faiz Y. Bhora.
Introduction:
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Iatrogenic tracheal stenosis (ITS) may occur in up to 20% of patients after prolonged intubation.
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Management is mainly interventional, with options including tracheal resection & reconstruction, bronchoscopic dilation, laser therapy, spray cryotherapy or airway stent placement.
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Adjunctive medical therapies to consolidate the benefit of surgery have been explored, but with limited success.
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To characterize gene expression patterns in granulation tissue of patients with ITS.
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Tissue Sampling: Biopsies of granulation tissue were collected longitudinally from two patients with severe ITS, with tracheostomies.
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Samples were taken immediately prior to endoscopic balloon dilation & spray cryotherapy, 4-6 weeks apart.
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Tissue RNA Sequencing: Using Illumina HiSeq
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Gene Expression Analysis: CLC Genomics (Qiagen)
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Functional Annotations: DAVID platform/KEGG pathways
Patient 1 (Poor Responder)
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Clinical Course: Redeveloped severe tracheal stenosis after both endoscopic treatments, necessitating continued indwelling tracheostomy tube
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Molecular Pathways: ↑ Cell-Cell Adhesion, ↑ Cellular Hyperproliferation, ↑ Inflammation
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Molecular Targets: IL36, CASP14, EPGN, KRTDAP, SLC6A11, GJB6, CXCL10 & 11
Patient 2 (Partial Responder)
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Clinical Course: Redeveloped mild tracheal stenosis after first endoscopic intervention, with adequate airway patency to allow for airway decannulation.
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Molecular Pathways & Targets: ↑ Oxygen Transport, ↑ Tissue Remodeling
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Molecular Targets: CDH6, C1QL1, CD70, MMP12, TRIM58, SOX4, GAL3ST1
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Treatment non-response in ITS is characterized by molecular profiles of dysregulated tissue growth and inflammatory response, with distinct molecular signatures unique to the clinical course of each patient.
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This open avenues to the multimodal management of ITS, with a combination of endoscopic treatment and novel, personalized biologics targeting key molecular pathways.