Evidence map›Paper›PMID 39314676›Full record

ArticleTherapeutic advances in chronic disease2024

Deep and unbiased proteomics, pathway enrichment analysis, and protein-protein interaction of biomarker signatures in migraine.

Yohannes W Woldeamanuel, Bharati M Sanjanwala, Robert P Cowan

Registry-linked trialAbstract read
In one paragraph

Article in Therapeutic advances in chronic disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03231241 (SunStar Project to Explore the Chronification Process in Headache Through Functional Imaging, Deep Phenotyping, and Analysis of CSF of Blood Products), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03231241 recruitingnot on this map

SunStar Project to Explore the Chronification Process in Headache Through Functional Imaging, Deep Phenotyping, and Analysis of CSF of Blood Products

TypeobservationalSponsorStanford UniversityRan2014 to 2026Enrolled700ConditionsChronic Daily Headache, Chronic Migraine
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. The serum proteomic profile in patients with migraine.Frontiers in molecular neuroscience · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Yohannes W WoldeamanuelDivision of Headache, Department of Neurology, Mayo Clinic Arizona, 6161 E. Mayo Blvd, Phoenix, AZ, USA.ORCID https://orcid.org/0000-0003-4879-6098
Bharati M SanjanwalaDivision of Headache and Facial Pain, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA, USA.
Robert P CowanDivision of Headache and Facial Pain, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA, USA.

Funding

Feasibility, Acceptability, and Pilot Testing of a Behavioral Intervention for Chronic MigraineK01NS124911 · NINDS · STANFORD UNIVERSITY · PI WOLDEAMANUEL, YOHANNES WOUBISHET · 2021 to 2025
$1.2M
NINDS NIH HHS K01 NS124911
6 · The paper itself

Abstract

Background: Currently, there are no biomarkers for migraine. Objectives: We aimed to identify proteomic biomarker signatures for diagnosing, subclassifying, and predicting treatment response in migraine. Design: This is a cross-sectional and longitudinal study of untargeted serum and cerebrospinal fluid (CSF) proteomics in episodic migraine (EM; Methods: We developed classification models for biomarker identification and natural clusters through unsupervised classification using agglomerative hierarchical clustering (AHC). Pathway analysis of differentially expressed proteins was performed. Results: Of 405 CSF proteins, the top five proteins that discriminated between migraine patients and HC were angiotensinogen, cell adhesion molecule 3, immunoglobulin heavy variable (IGHV) V-III region JON, insulin-like growth factor binding protein 6 (IGFBP-6), and IGFBP-7. The top-performing classifier demonstrated 100% sensitivity and 75% specificity in differentiating the two groups. Of 229 serum proteins, the top five proteins in classifying patients with migraine were immunoglobulin heavy variable 3-74 (IGHV 3-74), proteoglycan 4, immunoglobulin kappa variable 3D-15, zinc finger protein (ZFP)-814, and mediator of RNA polymerase II transcription subunit 12. The best-performing classifier exhibited 94% sensitivity and 92% specificity. AHC separated EM, CM, and HC into distinct clusters with 90% success. Migraine patients exhibited increased ZFP-814 and calcium voltage-gated channel subunit alpha 1F (CACNA1F) levels, while IGHV 3-74 levels decreased in both cross-sectional and longitudinal serum analyses. ZFP-814 remained upregulated during the CM-to-EM reversion but was suppressed when CM persisted. CACNA1F was pronounced in CM persistence. Pathway analysis revealed immune, coagulation, glucose metabolism, erythrocyte oxygen and carbon dioxide exchange, and insulin-like growth factor regulation pathways. Conclusion: Our data-driven study provides evidence for identifying novel proteomic biomarker signatures to diagnose, subclassify, and predict treatment responses for migraine. The dysregulated biomolecules affect multiple pathways, leading to cortical spreading depression, trigeminal nociceptor sensitization, oxidative stress, blood-brain barrier disruption, immune response, and coagulation cascades. Trial registration: NCT03231241, ClincialTrials.gov.

Indexed as

biomarkersmigrainepathway enrichmentproteomics

Identifiers

PMID39314676
PMCPMC11418313

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.