Dataset Information

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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Publications

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]

PMID: 35885999

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Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

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Dataset Information

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

Publications

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

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