Dynamic changes of urine proteome in a Walker 256 tumor-bearing rat model

Abstract

Despite advances in cancer treatments, early diagnosis of cancer is still the most promising way to improve outcomes. Without homeostatic control, urine reflects systemic changes in the body and can potentially be used for early detection of cancer. In this study, a tumor-bearing rat model was established by subcutaneous injection of Walker 256 cells. Urine samples from tumor-bearing rats were collected at five time points during cancer development. Dynamic urine proteomes were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Several urine proteins that changed at multiple time points were selected as candidate cancer biomarkers and were further validated by multiple reaction monitoring (MRM) analysis. It was found that the urinary protein patterns changed significantly with cancer development in a tumor-bearing rat model. A total of 10 urinary proteins (HPT, APOA4, CO4, B2MG, A1AG, CATC, VCAM1, CALB1, CSPG4, and VTDB) changed significantly even before a tumor mass was palpable, and these early changes in urine could also be identified with differential abundance at late stages of cancer. Our results indicate that urine proteins could enable early detection of cancer at an early onset of tumor growth and monitoring of cancer progression.

Urine is a noninvasive and attractive biofluid for biomarker research, and has the potential to reflect early and small pathological changes in the body. Urine proteins changed significantly with cancer development in a tumor-bearing rat model. Our results indicate that urine proteins could enable early detection of cancer at an early onset of tumor growth and monitoring of cancer progression.

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