Early urinary protein changes during tumor formation in a NuTu-19 tail vein injection rat model

Jing Wei,Yuhang Huan,Youhe Gao,Wenshu Meng,Na Ni

doi:10.1038/s41598-020-68674-z

Jing Wei, Yuhang Huan + Show 3 more

Open Access

https://doi.org/10.1038/s41598-020-68674-z

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Abstract

Early detection of cancer is essential for effective intervention. Urine has been used to reflect early changes in various tumor-bearing models. However, urine has not been used to predict whether tumors will form in animal models. In this study, a cancer model was established by tail vein injection of 2 million NuTu-19 tumor cells. Urine samples were randomly selected from tumor-forming and non-tumor-forming rats on day 0/12/27/39/52 and were analyzed by label-free and parallel reaction monitoring targeted proteomic quantitative analyses. In tumor-forming rats, differential proteins were associated with tumor cell migration, TGF-β signaling and the STAT3 pathway. A total of 9 urinary proteins showed significant changes in the early phase of lung tumor formation in all eight tumor-bearing rats. Differential proteins in non-tumor-forming rats were associated with glutathione biosynthesis, IL-12 signaling and vitamin metabolism. A total of 12 urinary proteins changed significantly in the early phase in all seven non-tumor-forming rats. Our small-scale pilot study indicated that (1) the urinary proteome reflects early changes during lung tumor formation and that (2) the urinary proteome can distinguish early tumor-forming rats from non-tumor-forming rats.

Highlights

Detection of cancer is essential for effective intervention
The urinary proteomes were first analyzed with a label-free proteomic method, and candidate biomarkers in tumor-forming and non-tumor-forming rats were validated by parallel reaction monitoring (PRM) targeted quantification
95% viable tumor cells were used for the following tail vein injection

Summary

Introduction

Detection of cancer is essential for effective intervention. Urine has been used to reflect early changes in various tumor-bearing models. We used urinary proteomes to examine early alterations that occur before pathological changes or clinical manifestations in various tumor-bearing animal models, such as a subcutaneous Walker 256 (W256) rat m odel[11], an intracerebral W256 rat m odel[12], a glioma rat m odel[13], and a W256 lung metastasis rat model[14]. There have been no studies on whether urine can be used to predict tumor formation In this experiment, we sought to analyze the differences in urinary proteomes between animals that formed tumors and those that did not. A cancer rat model was established through tail vein injection of two million NuTu-19 tumor cells. This study was designed to identify early urinary proteome changes in tumor-forming and non-tumor-forming rats.

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