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Antibody-based biomarker discovery

The resource of antibodies and protein profiling data created as part of the HPA program has been used for biomarker discovery programs using pathology-based immunohistochemistry. More than 140 scientific manuscripts have been published in the field of pathology, coauthored by members of the HPA effort. This includes biomarkers for both cancer diagnostics and biomarkers with prognostic value to predict clinical outcome in cancer patients.

In addition, the HPA consortium also explored the proteins circulating in blood and other body fluids to find possible biomarkers providing information about health and disease states on both a systemic and organ-specific level. Antibodies and protein fragments generated in the HPA have been used to develop and apply multiplexed assays for discovering disease-related proteins. Together with technical and biological validation schemes, the studies conducted across different disease areas highlight the value of studying proteins as biomarkers.

Key publication

  • Magnusson K et al., SATB2 in combination with cytokeratin 20 identifies over 95% of all colorectal carcinomas. Am J Surg Pathol. (2011)
    PubMed: 21677534 DOI: 10.1097/PAS.0b013e31821c3dae

  • Schwenk JM et al., Toward next generation plasma profiling via heat-induced epitope retrieval and array-based assays. Mol Cell Proteomics. (2010)
    PubMed: 20682762 DOI: 10.1074/mcp.M110.001560

Other selected publications

  • Jögi A et al., Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer. Mod Pathol. (2009)
    PubMed: 19734850 DOI: 10.1038/modpathol.2009.124

  • Gremel G et al., A systematic analysis of commonly used antibodies in cancer diagnostics. Histopathology. (2014)
    PubMed: 24330150 DOI: 10.1111/his.12255

  • Bachmann J et al., Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria. PLoS Pathog. (2014)
    PubMed: 24743550 DOI: 10.1371/journal.ppat.1004038

  • Ayoglu B et al., Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies. EMBO Mol Med. (2014)
    PubMed: 24920607 DOI: 10.15252/emmm.201303724

  • Häussler RS et al., Systematic Development of Sandwich Immunoassays for the Plasma Secretome. Proteomics. (2019)
    PubMed: 31278833 DOI: 10.1002/pmic.201900008

Figure legend: Examples of tissue-biomarker discovery efforts, including (A) SATB2 as a diagnostic marker for colorectal cancer, (B) T-Pit transcription factor for diagnostics of pituitary neuroendocrine tumors, (C) RBM3 as a prognostic cancer biomarker for breast and ovarian cancer, and (D) ASRGL1 as a prognostic marker for endometrial cancer.

Key facts

  • Multiplexed immunoassays for protein profiling have been performed across multiple diseases
  • Systematic assays for plasma, serum, and cerebrospinal fluid have been performed, allowing analysis of thousands of protein targets
  • More than 80 peer-reviewed, body-fluid biomarker studies have been published by HPA researchers
  • Protein expression data from the HPA has been used for cancer biomarker discovery
  • Prognostic markers based on expression data were identified for several cancers
  • More than 140 peer-reviewed publications in pathology have been published by HPA researchers