Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

et al. 2019

Cancer Medicine

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Background Patients with primary and metastatic brain cancer have an extremely poor prognosis, mostly due to the late diagnosis of disease. Urine, which lacks homeostatic mechanisms, is an ideal biomarker source that accumulates early and highly sensitive changes to provide information about the early stage of disease. Methods A rat model mimicking the local tumor growth process in the brain was established with intracerebral Walker 256 (W256) cell injection. Urine samples were collected on days 3, 5, and 8 after injection, and then analyzed by liquid chromatography coupled with tandem mass spectrometry. Results In the intracerebral W256 model, no obvious clinical manifestations or abnormal magnetic resonance imaging (MRI) signals were found on days 3 or 5; at these time points, 9 proteins were changed significantly in the urine of all eight tumor rats. On day 8, when tumors were detected by MRI, 25 differential proteins were identified, including 10 that have been reported to be closely related to brain metastasis or primary tumors. The differential urinary proteome was compared with those from the subcutaneous W256 model and the intracerebral C6 model. Few differential proteins overlapped, and specific differential protein patterns were observed among the three models. Conclusions These findings demonstrate that early changes in the urine proteome can be detected in the intracerebral W256 model. The urinary proteome can reflect the difference when tumor cells with different growth characteristics are inoculated into the brain and when identical tumor cells are inoculated into different areas, specifically, the subcutis and the brain.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Zhang

et al. 2019

Cancer Medicine

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“…Urine, a new source of sensitive biomarkers for noninvasive analysis, has been shown to provide clues for the early diagnosis of disease in a variety of animal models in our previous work [37][38][39][40][41][42]. The W256 breast carcinoma cell line has been used for a rat model of brain metastases that is similar in histopathology to patients with brain metastases [43][44][45][46].…”

Section: Urinary Candidate Biomarker Validation and Analysismentioning

confidence: 99%

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Zhang

et al. 2018

Preprint

Self Cite

Patients with primary and metastatic brain cancer have an extremely poor prognosis, mostly due to the late diagnosis of disease. Urine, which lacks homeostatic mechanisms, is an ideal biomarker source that accumulates early and highly sensitive changes to provides information about the early stage of disease. A rat model mimicking the local tumor growth process in the brain was established with intracerebral Walker 256 (W256) cell injection. Urine samples were collected on days 3, 5 and 8 after injection and then analyzed by LC-MS/MS. In the intracerebral W256 model, no obvious clinical manifestations changes or abnormal MRI signals were found on days 3 and 5; at these time points, nine proteins were changed significantly in the urine of all 8 tumor rats. On day 8, when tumors were detected by MRI, twenty-five differential proteins were identified, including 10 proteins that have been reported to be closely related to tumor metastasis or brain tumors. The differential urinary proteomes were compared with those from the subcutaneous W256 model and the intracerebral C6 model. Few differential proteins overlapped. Specific differential protein patterns were observed among the three models, indicating that the urinary proteome can reflect the difference when tumor cells with different growth characteristics are inoculated into the brain and when identical tumor cells are inoculated into different areas, specifically, the subcutis and the brain.

“…The use of animal models minimizes external influence factors, and differential urinary proteins found in animal models are more likely to be directly associated with related diseases. According to this strategy, our laboratory has applied different types of animal models, such as subcutaneous tumor-bearing model [4] , pulmonary fibrosis [5] , glioma [6] , liver fibrosis [7] , Alzheimer's disease [8] , chronic pancreatitis [9] and myocarditis [10] , to search for early biomarkers before the appearance of pathology changes and clinical manifestations.…”

Section: Introductionmentioning

confidence: 99%

Urine proteome changes in rats with approximately ten tumor cells subcutaneous inoculation

Wei

Gao

2019

Preprint

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Biomarkers are changes associated with the disease. Without homeostatic control, urine accumulates very early changes and is an ideal biomarker source. Usually, we performed urinary biomarker studies involving at least thousands of tumor cells. But no tumor starts from a thousand tumor cells. Can we observe any urine proteome changes in rats with approximately ten tumor cells subcutaneous inoculation? Here, we serially diluted Walker-256 carcinosarcoma cells to a concentration of 10 2 /mL and subcutaneously inoculated 0.1 mL of these cells into nine rats. Urine proteomes on days 0, 13 and 21 were profiled by LC-MS/MS analysis and studied with unsupervised clustering analysis. Samples at three time points were almost clustered together, indicating a good consistency in these nine rats. 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. Our results indicated that 1) the urine proteome reflects changes associated with cancer even with 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.