Proteomic study of sera from patients with bladder cancer: usefulness of S100A8 and S100A9 proteins.

To effectively obtain tumour-specific markers, fractionated proteins obtained using reversed-phase high- performance liquid chromatography for patient-matched pre- and post-operative sera from bladder cancer patients were compared by two-dimensional gel electrophoresis. The usefulness of the identified proteins was confirmed immunohistochemically. S100A8 and S100A9 were identified as tumour-associated proteins. The increased immunoreactive expression of S100A8 protein was associated with bladder wall muscle invasion of the tumour and cancer-specific survival (p<0.05), and the increased immunoreactive expression of S100A9 protein was associated with the tumour grade (p<0.05). In addition, increased expressions of both proteins was associated with recurrence-free survival at a median follow-up of 32.9 months (both p<0.05). On multivariate analysis, the expression of S100A8 was a significant predictor of recurrence (p<0.05). These findings may help to identify biologically aggressive cancers and, thus, patients who might benefit from more intensive adjuvant therapy. Bladder cancer, responsible for an estimated 14,100 deaths in the USA alone in 2008, as well as 68,810 expected new cases, is the fifth most common cancer in men and women in the United States (1). Urothelial carcinoma (UC) represents over 90% of all bladder cancers, and approximately 75% of these are papillary tumours localized in the urothelium (superficial, pTa) or lamina propria (pT1). Even in pTa tumours, about 70% of cases recur even after transurethral resection, 30-50% of which progress to higher-grade tumours (2). In tumours initially presenting with bladder muscle invasion, 50% of patients treated endoscopically show recurrence within 2 years after treatment (3), and two-thirds of patients die within 5 years (4). In addition, patient outcome is strongly correlated with the tumour stage at the initial diagnosis. The development of new, highly effective and accurate screening tests that could detect most cancers even at an early stage, before metastasis has occurred, might markedly decrease cancer death rates (5).