Abstract

In this report, the urinary proteome from a patient-derived xenograft (PDX) model was examined at the peptide level to study the origins of urinary proteins in tumor-bearing nude mice. Urine was collected from PDX mice before and after colorectal tumor implantation. A total of 4,318 unique peptides were identified, and 78 unambiguous human-origin peptides were discerned in the PDX model urine. Unlike the differential urinary protein composition of tumor-bearing immunocompetent rat models, the differential urinary proteins in the PDX model did not include host immune-response proteins. This study demonstrates that tumor-secreted proteins can be observed in the urine proteome of the PDX model. However, immune-response proteins, which are very early candidate tumor biomarkers, are not present in the urine of PDX model mice; this absence is due to immune deficiency. Therefore, immunodeficient animals may not be suitable models for searching for early immunity-associated tumor biomarkers in the urine.

Highlights

  • Many reports have found candidate biomarkers in the urine for the very early stages of disease

  • Changes in the urinary proteome of rats injected with C6 glioma cells in the brain were observed before the tumors could be detected by magnetic resonance imaging (MRI)

  • In the patient-derived xenograft (PDX) model[11], human-origin tumors can grow due to the absence of normal T cell immunity

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Summary

Introduction

Many reports have found candidate biomarkers in the urine for the very early stages of disease. Several urinary proteins have been shown to change in a rat model of chronic obstructive pulmonary disease (COPD), and some of the candidate markers are associated with COPD7. Changes in the urinary proteome of rats injected with C6 glioma cells in the brain were observed before the tumors could be detected by magnetic resonance imaging (MRI). Many of these differential urinary proteins were previously reported to be associated with glioma[10]. The identified peptides were compared at the peptide level[12]

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