Background: Bladder cancer is the most common urological malignancy with a high tendency for progression and recurrence. So far, no reliable diagnostic marker is present with 100% sensitivity and specificity. Netrins are related to laminin proteins, and were first discovered to be involved in neural development. After that, they were found in other organs of the body and several studies stated that they have implicated in cancer progression.
Purpose: This study aimed at investigating the netrin-1 gene expression in bladder cancer tissues, in addition to the possibility of using urinary netrin-1 as a marker for muscle invasion diagnosis in bladder cancer cases.
Methods: Netrin-1 gene expression in bladder cancer tissue was detected in this study by real-time polymerase chain reaction. Moreover, netrin-1 protein was measured in tissue and urinary deposit samples by western blotting.
Results: The results of this study revealed that netrin-1 is expressed in bladder cancer and control tissues, with a strong positive correlation between netrin-1 in tissues and urinary netrin-1 (rs = 0.762, P < 0.0005). Receiver operating characteristic curve analysis confirmed the muscle-invasion diagnostic value of urinary netrin-1 with bladder cancer cases, providing an area under the curve equals to 0.758 (95% confidence interval, 0.630-0.886, P < 0.0005), with 96% sensitivity and 67% specificity. Bladder cancer patients had been included to examine risk factors for local recurrence, distant metastasis, and death. Cox regression models showed that netrin-1 gene expression, tumor size, and age are positive predictor markers for local tumor recurrence. Age is a predictor for distant metastasis, and tumor stage is a predictor for death.
Conclusion: Urinary netrin-1 can be used as a promising biomarker for diagnosis of muscle invasion, which may help in the follow up of non-invasive tumors. In addition, tissue netrin-1 expression may serve as a predictor of local tumor recurrence.
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