Development and Evaluation of Antibody Proteomics Technology for Rapid and Comprehensive Identification of Potential Biomarkers and Therapeutic Targets

Our plain-English summary of Development and Evaluation of Antibody Proteomics Technology for Rapid and Comprehensive Identification of Potential Biomarkers and Therapeutic Targets, by K. Nagano (Biological & Pharmaceutical Bulletin, 2018).

The study

• Author: K. Nagano
• Journal: Biological & Pharmaceutical Bulletin
• Published: 2018;41(5):663-669
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Proteomics-based analyses are powerful means of identifying potentially useful proteins in the initial stage of drug development. Technological developments in the field of proteomics, and increases in the sensitivity of MS analyses, now facilitate identification and examination of increasingly small amounts of proteins that are differentially expressed in diseased versus normal tissues and can be candidate biomarkers or therapeutic targets. However, the current approach is for candidate proteins to be prioritized by research interest and then validated one by one; this is very inefficient. To address this issue, we have developed what we refer to as "antibody proteomics technology," which uses a phage antibody library and tissue microarray analysis to rapidly and comprehensively isolate monoclonal antibodies against candidate proteins for the identification of potential biomarkers and therapeutic targets. In our validation of this technology, we successfully identified oxysterol binding protein-like 5 and calumenin as potential biomarkers related to metastasis in lung cancer, annexin A4 as a potential biomarker related to cisplatin resistance in malignant mesothelioma, and Eph receptor A10 as a potential therapeutic target in breast cancer, including refractory breast cancer. These findings suggest that antibody proteomics technology has the potential to become a fundamental technology in drug discovery for the development of novel biomarkers and therapeutic targets.

In plain English

This article was a review in which the author described earlier laboratory work by the author's research group on a method the author called "antibody proteomics technology". The method searches for proteins that differ between diseased and normal cells, makes antibodies against them using a phage antibody library, and then tests them on tissue samples. In lung adenocarcinoma, two proteins, OSBPL5 and calumenin, were more common in tumor samples with lymph node metastasis. Of 46 samples, 15 were positive for both proteins, and 12 of those 15 (80%) were metastasis-positive. In malignant mesothelioma, annexin A4 was higher in malignant tissue than in benign or normal mesothelial tissue. In mesothelioma cell lines, lowering annexin A4 made cells more sensitive to the drug cisplatin, and raising it made them less sensitive. In breast cancer, the protein EphA10 was found in 73 of 120 tumor samples (61%), and an antibody against it slowed tumor growth in mice. Asbestos exposure itself was not studied. The author concluded that the technology has the potential to become a fundamental drug-discovery tool.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of the author's own group's earlier laboratory studies (cell lines, tissue microarrays, mouse xenograft experiments)
• Who was studied: Lung work: two human lung adenocarcinoma cell lines and 46 lung tumor samples. Mesothelioma work: five mesothelioma cell lines (H28, H2052, H2452, H226, MSTO-221H) plus malignant mesothelioma, benign mesothelioma and normal mesothelial tissues (numbers not given). Breast work: SKBR3 breast cancer cells versus 184A1 normal cells, 120 breast cancer tissue samples, 36 normal tissue types, and xenograft mice.
• Exposure: No asbestos exposure was studied. The mesothelioma work compared mesothelioma cells that were highly or only slightly susceptible to the drug cisplatin. Asbestos is mentioned only as background.
• Main results:
  • Lung cancer: OSBPL5 and calumenin expression ratios were significantly higher in lymph node metastasis-positive tissue samples than in metastasis-negative samples (p=0.0156 and p=0.0055).
  • Lung cancer: 15 of 46 lung tumor samples were positive for both proteins, and 12 of these 15 (80%) were lymph node metastasis-positive.
  • Malignant mesothelioma: among eight candidate proteins, annexin A4 expression was higher in malignant mesothelioma tissues than in benign mesothelioma tissues and normal mesothelial tissues.
  • Mesothelioma cell lines: cisplatin IC50 values were 80.0 µM in non-transfected H28 cells, 71.8 µM with control siRNA and 15.5 µM with ANXA4-siRNA. In H2052 cells they were 55.2 µM with the control vector and 89.7 µM with the ANXA4 vector. The authors read this as susceptibility rising when annexin A4 was reduced and falling when it was increased.
  • Breast cancer: EphA10 was positive in 73 of 120 tissue samples (61%): luminal A 22 of 41 (54%), luminal B 25 of 37 (68%), Her2-enriched 16 of 27 (64%), triple-negative 10 of 15 (67%).
  • Breast cancer: among 36 normal tissue types, EphA10 was found only in the testes. In mice, anti-EphA10 antibody significantly suppressed tumor growth in a dose-dependent manner.
• The authors' conclusion: The author concluded that annexin A4 was associated with cisplatin resistance in mesothelioma cells and is a potential biomarker for telling cisplatin responders from non-responders. The author further concluded that antibody proteomics technology has the potential to become a fundamental technology in drug discovery.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Monoclonal, Metastasis, Lung Cancer, Cisplatin, Malignant Mesothelioma, Discovery.

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