Differential regulation of urine proteins in urothelial neoplasm

Urothelial neoplasm of the urinary bladder has a high rate of multifocality and recurrence. To understand this we first need to understand the changes in the molecular level that distinguishes a normal individual from a patient and also a low grade neoplasm from a high grade. In this work we aim to study the urine proteome of Indian patients with urothelial neoplasm categorised on the basis of their p53 immunohistochemistry. The urine samples of pre-operative patients were subjected to two dimensional gel electrophoresis followed by densitometric analysis and spot identification using MALDI mass spectrometry. Our study shows that few proteins such as albumin, alpha 1 antitrypsin, apolipoprotein A1, transferrin, transthyretin, haptoglobin and haemoglobin β chain were upregulated and inter alpha trypsin inhibitor heavy chain was downregulated in the disease samples. Further we have reported that some of these proteins show an association with disease severity. The present study marks the first step in the identification of new diagnostic markers as well as therapeutic targets.

Biological significance: Bladder carcinoma is the ninth most common cancer worldwide. It has gained attention within both clinicians and cancer biologists because of its recurrence and mortality rate. Identifying the prognostic factors of progression is a challenge, so that high risk patients who may be a candidate for a radical cystectomy may be identified. In this study we have attempted to study the changes observed in the urinary protein levels of urothelial neoplasm patients. The samples were graded based on p53 immunohistochemistry staining. We have reported eight (8) proteins, mostly highly abundant; those have exhibited differential regulation in case of diseased samples. This study is first of its kind that associates the changes in the urinary protein levels to that of the severity of the disease. We believe that the findings can be used as a stepping stone in the development of a noninvasive prognostic tool for the disease. This article is part of a Special Issue entitled: Proteomics in India.