Affiliation:
1. Department of Biochemistry and Molecular Biology, Beijing Normal University, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing, China
Abstract
Background
Biomarkers are changes associated with the disease. Urine is not subject to homeostatic control and therefore accumulates very early changes, making it an ideal biomarker source. Usually, we have performed urinary biomarker studies involving at least thousands of tumor cells. However, no tumor starts from a thousand tumor cells. We therefore examined urine proteome changes in rats subcutaneously inoculated with approximately ten tumor cells.
Methods
Here, we serially diluted Walker-256 carcinosarcoma cells to a concentration of 102/mL and subcutaneously inoculated 0.1 mL of these cells into nine rats. The urine proteomes on days 0, 13 and 21 were analyzed by liquid chromatography coupled with tandem mass spectrometry.
Results
Hierarchical clustering analysis showed that the urine proteome of each sample at three time points were clustered into three clusters, indicating the good consistency of these nine rats when inoculated with the same limited tumor cells. Differential proteins on days 13 and 21 were mainly associated with cell adhesion, autophagic cell death, changes in extracellular matrix organization, angiogenesis, and the pentose phosphate pathway. All of these enriched functional processes were reported to contribute to tumor progression and could not be enriched through random allocation analysis.
Conclusions
Our results indicated that (1) the urine proteome reflects changes associated with cancer even with only approximately ten tumor cells in the body and that (2) the urine proteome reflects pathophysiological changes in the body with extremely high sensitivity and provides potential for a very early screening process of clinical patients.
Funder
National Key Research and Development Program of China
Beijing Natural Science Foundation
Beijing Cooperative Construction Project
Beijing Normal University
Union Medical College Hospital
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
8 articles.
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