ArticlePloS one2014
Absolute quantitation of Met using mass spectrometry for clinical application: assay precision, stability, and correlation with MET gene amplification in FFPE tumor tissue.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- Personalized Antibodies for Gastroesophageal Adenocarcinoma (PANGEA): A Phase II Study Evaluating an Individualized Treatment Strategy for Metastatic Disease.Cancer discovery · 2021Trial
- Trial
- Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial.The Lancet. Oncology · 2017Trial
- Mass spectrometry-based proteomics of FFPE tissues: progress, limitations, and clinical translation barriers.Clinical proteomics · 2025Review
- EGFR-directed antibodies promote HER2 ADC internalization and efficacy.Cell reports. Medicine · 2024Article
- Biomarker Identification through Proteomics in Colorectal Cancer.International journal of molecular sciences · 2024Review
- Clinical Proteomics for Solid Organ Tissues.Molecular & cellular proteomics : MCP · 2023Article
- Biomarker Analysis of Formalin-Fixed Paraffin-Embedded Clinical Tissues Using Proteomics.Biomolecules · 2023Review
- Article
- Quantitation of ligand is critical for ligand-dependent MET signalling activation and determines MET-targeted therapeutic response in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Article
- Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Observational
- MET-dependent solid tumours - molecular diagnosis and targeted therapy.Nature reviews. Clinical oncology · 2020Review
- EGFR Blockade Reverts Resistance to KRASCancer discovery · 2020Article
- Review
- Targeted multiplex proteomics for molecular prescreening and biomarker discovery in metastatic colorectal cancer.Scientific reports · 2019Article
- MET activation confers resistance to cetuximab, and prevents HER2 and HER3 upregulation in head and neck cancer.International journal of cancer · 2019Article
- Development and interlaboratory evaluation of a NIST Reference Material RM 8366 for EGFR and MET gene copy number measurements.Clinical chemistry and laboratory medicine · 2019Article
- The Relevance of Mass Spectrometry Analysis for Personalized Medicine through Its Successful Application in Cancer "Omics".International journal of molecular sciences · 2019Review
- Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Data-Independent Acquisition Mass Spectrometry To Quantify Protein Levels in FFPE Tumor Biopsies for Molecular Diagnostics.Journal of proteome research · 2019Article
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOverexpression of Met tyrosine kinase receptor is associated with poor prognosis. Overexpression, and particularly MET amplification, are predictive of response to Met-specific therapy in preclinical models. Immunohistochemistry (IHC) of formalin-fixed paraffin-embedded (FFPE) tissues is currently used to select for 'high Met' expressing tumors for Met inhibitor trials. IHC suffers from antibody non-specificity, lack of quantitative resolution, and, when quantifying multiple proteins, inefficient use of scarce tissue.
methodsAfter describing the development of the Liquid-Tissue-Selected Reaction Monitoring-mass spectrometry (LT-SRM-MS) Met assay, we evaluated the expression level of Met in 130 FFPE gastroesophageal cancer (GEC) tissues. We assessed the correlation of SRM Met expression to IHC and mean MET gene copy number (GCN)/nucleus or MET/CEP7 ratio by fluorescence in situ hybridization (FISH).
resultsProteomic mapping of recombinant Met identified 418TEFTTALQR426 as the optimal SRM peptide. Limits of detection (LOD) and quantitation (LOQ) for this peptide were 150 and 200 amol/µg tumor protein, respectively. The assay demonstrated excellent precision and temporal stability of measurements in serial sections analyzed one year apart. Expression levels of 130 GEC tissues ranged (<150 amol/µg to 4669.5 amol/µg. High correlation was observed between SRM Met expression and both MET GCN and MET/CEP7 ratio as determined by FISH (n = 30; R2 = 0.898). IHC did not correlate well with SRM (n = 44; R2 = 0.537) nor FISH GCN (n = 31; R2 = 0.509). A Met SRM level of ≥1500 amol/µg was 100% sensitive (95% CI 0.69-1) and 100% specific (95% CI 0.92-1) for MET amplification.
conclusionsThe Met SRM assay measured the absolute Met levels in clinical tissues with high precision. Compared to IHC, SRM provided a quantitative and linear measurement of Met expression, reliably distinguishing between non-amplified and amplified MET tumors. These results demonstrate a novel clinical tool for efficient tumor expression profiling, potentially leading to better informed therapeutic decisions for patients with GEC.
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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.