Renal cell carcinoma (RCC) ranks the first death rate among the urogenital tumors, whereas its incidence follows the incidences of prostate and bladder cancer. The diagnosis of RCC at early stages allows immediately undertaking appropriate treatment, which significantly increases patients' survival rate. Early and accurate diagnosis avoids inadequate treatment, provides the disease progression forecast, and permits to apply more efficient therapy. Unfortunately, the small renal tumors are usually asymptomatic resulting in the late diagnosis and, therefore, low efficacy of treatment. Thus, sensible and preventive biomarkers are essential for early RCC detection and monitoring of its progression. So far, many attempts were performed aimed at recognizing novel informative kidney tumor biomarkers applicable for early detection of the disease and possessing prognostic and predictive capabilities. This review summarizes recent advances in renal tumor biomarkers recognition, their diagnostic and prognostic values, and clinical feasibility.
The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.
It is suggested that activated CD44+ cells play a profibrogenic role in the pathogenesis of active glomerulopathies. Complement activation is also involved in renal fibrogenesis. The aim of the study was to evaluate the role of the activation of CD44+ cells in the kidney tissue and complement components’ filtration to the urine as factors of renal tissue fibrosis in patients with glomerulopathies. In total, 60 patients with active glomerulopathies were included in our study: 29 patients with focal segmental glomerulosclerosis (FSGS), 10 patients with minimal change disease (MCD), 10 patients with membranous nephropathy (MN), and 11 patients with IgA nephropathy. The immunohistochemical peroxidase method was used to study the expression of CD44+ in kidney biopsies. Components of complement were analyzed in urine by the multiple reaction monitoring (MRM) approach using liquid chromatography. Strong CD44 expression was noted predominantly in PEC and mesangial cells (MC) in patients with FSGS, and to a lesser extent, in patients with MN and IgA nephropathy, and it was absent in patients with MCD. Expression of profibrogenic CD44+ in glomeruli correlated with the levels of proteinuria and complement C2, C3, and C9 components, and CFB and CFI in urine. The CD44+ expression scores in the renal interstitium correlated with the level of C3 and C9 components of complement in the urine and the area of tubulo-interstitial fibrosis. The strongest expression of CD44+ was found in the glomeruli (MC, PEC, and podocytes) of patients with FSGS compared with other glomerulopathies. The CD44 expression score in the glomeruli and interstitium is associated with high levels of complement components in the urine and renal fibrosis.
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