Proteomics

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Global Phospho-Proteomic Profiling of Pathway-Level Molecular Alterations in Barrett’s Esophagus


ABSTRACT: In the present study, we applied deep, quantitative mass-spectrometry to clinical samples (Barrett’s esophagus and matched adjacent normal biopsies) to gain a mechanistic understanding of the molecular pathways associated with disease progression. From our rich LC/MS profiles, we identified a robust proteomic signature that was able to correctly classify independent samples on disease status. Projection of this same signature against EAC tumor profiles was strongly predictive of survival outcomes, while subsequent comparative analysis with published BE transcriptomic profiles provided independent evidence in support of these results. Further, our phosphoproteomic analysis revealed signaling pathways specifically and significantly altered in BE relative to paired controls, providing some mechanistic insights into the cellular dysregulation of key components of specific processes that likely drives disease progression.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Barrett's Esophagus, Esophagus

DISEASE(S): Barrett's Esophagus

SUBMITTER: Jarrod Moore  

LAB HEAD: Andrew Emili

PROVIDER: PXD023293 | Pride | 2022-08-11

REPOSITORIES: Pride

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Pilot Study Showing Feasibility of Phosphoproteomic Profiling of Pathway-Level Molecular Alterations in Barrett's Esophagus.

Moore Jarrod J   Hekman Ryan R   Blum Benjamin C BC   Lawton Matthew M   Lehoux Sylvain S   Stachler Matthew M   Pleskow Douglas D   Sawhney Mandeep S MS   Cummings Richard D RD   Emili Andrew A   Qureshi Alia A  

Genes 20220707 7


(1) Background: Barrett's esophagus is a major risk factor for esophageal adenocarcinoma. In this pilot study, we employed precision mass spectrometry to map global (phospho)protein perturbations in Barrett's esophagus lesions and adjacent normal tissue to glean insights into disease progression. (2) Methods: Biopsies were collected from two small but independent cohorts. Comparative analyses were performed between Barrett's esophagus samples and adjacent matched (normal) tissues from patients w  ...[more]

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