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Activity-based proteomics: identification of ABHD11 and ESD activities as potential biomarkers for human lung adenocarcinoma


Wiedl, T; Arni, S; Roschitzki, B; Grossmann, J; Collaud, S; Soltermann, A; Hillinger, S; Aebersold, R; Weder, W (2011). Activity-based proteomics: identification of ABHD11 and ESD activities as potential biomarkers for human lung adenocarcinoma. Journal of Proteomics, 74(10):1884-1894.

Abstract

Lung cancer is the leading cause of all cancer related deaths with a worldwide mortality of 1.2 million each year. The 5-year survival rate ranges from 80% in early stages to a dismal 5% in advanced disease. Prognosis is currently mostly determined based on the extension of disease at diagnosis. Thereby it has become evident that predicted and real outcomes can vary significantly, even for patients with the same stage of disease. Novel biomarkers with a reliable predictive significance are therefore clearly needed. In this study we implemented an activity-based, solely mass spectrometry dependent biomarker discovery platform. We investigated the role of serine hydrolase activities as potential biomarkers for human lung adenocarcinoma, the most common lung cancer subtype. Forty pairs of fresh frozen malignant and matching non-neoplastic lung tissues were analyzed and enzymatic activities linked to clinical follow-up data. We found that the activities of Abhydrolase domain-containing protein 11 and Esterase D predict the development of distant metastases and the presence of aggressive lung adenocarcinomas, respectively, in a statistically significant model. We conclude that serine hydrolase activities bear a predictive potential for human lung adenocarcinoma and that activity-based proteomics represents a powerful methodology in the search for novel disease biomarkers.

Lung cancer is the leading cause of all cancer related deaths with a worldwide mortality of 1.2 million each year. The 5-year survival rate ranges from 80% in early stages to a dismal 5% in advanced disease. Prognosis is currently mostly determined based on the extension of disease at diagnosis. Thereby it has become evident that predicted and real outcomes can vary significantly, even for patients with the same stage of disease. Novel biomarkers with a reliable predictive significance are therefore clearly needed. In this study we implemented an activity-based, solely mass spectrometry dependent biomarker discovery platform. We investigated the role of serine hydrolase activities as potential biomarkers for human lung adenocarcinoma, the most common lung cancer subtype. Forty pairs of fresh frozen malignant and matching non-neoplastic lung tissues were analyzed and enzymatic activities linked to clinical follow-up data. We found that the activities of Abhydrolase domain-containing protein 11 and Esterase D predict the development of distant metastases and the presence of aggressive lung adenocarcinomas, respectively, in a statistically significant model. We conclude that serine hydrolase activities bear a predictive potential for human lung adenocarcinoma and that activity-based proteomics represents a powerful methodology in the search for novel disease biomarkers.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:04 Jan 2012 10:23
Last Modified:05 Apr 2016 15:15
Publisher:Elsevier
ISSN:1874-3919
Publisher DOI:10.1016/j.jprot.2011.04.030
PubMed ID:21596165
Permanent URL: http://doi.org/10.5167/uzh-53102

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