Renal cell carcinoma (RCC), a human kidney cancer from the proximal tubular epithelium, accounts for about 3% of adult malignancies. Molecular and cytogenetic analysis have highlighted deletions, translocations, or loss of heterozygosity in the 3p21-p26, a putative RCC locus, as well as in 6q, 8p, 9pq, and 14pq. Studies on phenotypic expression of human kidney tissue and on post-translational modifications in RCC have not yet provided a marker for early renal cell carcinoma diagnosis. Current diagnostic methods do not help to detect the tumor before advanced stages. We therefore used two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to study normal and tumor kidney tissues in ten patients suffering from RCC. A human kidney protein map in the SWISS-2DPAGE database accessible through the ExPASy WWW Molecular Biology Server was established. Of 2789 separated polypeptides, 43 were identified by gel comparison, amino acid analysis, N-terminal sequencing, and/or immunodetection. The comparison between normal and tumor kidney tissues showed four polypeptides to be absent in RCC. One of them was identified as ubiquinol cytochrome c reductase (UQCR), whose locus has elsewhere been tentatively assigned to chromosome 19p12 or chromosome 22. A second polypeptide was identified as mitochondrial NADH-ubiquinone oxido-reductase complex I whose locus is located on chromosome 18p11.2 and chromosome 19q13.3. These result suggest that the lack of UQCR and of mitochondrial NADH-ubiquinone oxidoreductase complex I expression in RCC may be caused by unknown deletions, or by changes in gene transcription or translation. It might indicate that mitochondrial disfunction plays a major role in RCC genesis or evolution.

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Objective:We aimed to validate a panel of blood biomarkers to differentiate between ischemic stroke (IS) and intracerebral hemorrhage (ICH) in patients with suspected stroke.Methods:Patients with suspected stroke admitted within 4.5 hours after onset were enrolled. Blood samples were collected at hospital admission. Glial fibrillary acid protein (GFAP), retinol binding protein 4 (RBP-4), N-terminal pro B-type natriuretic peptide (NT-proBNP) and endostatin were measured by immunoassays. Cut-off points were obtained for 100% specificity for IS. A high-sensitivity assay to measure GFAP and rapid point-of-care tests (POCTs) to measure RBP-4 and NT-proBNP were used in subsets of patients. Biomarker panels were evaluated in another cohort of 62 stroke mimics.Results:A total of 189 patients (154 IS and 35 ICH) were enrolled. IS patients had higher RBP-4, NT-proBNP and endostatin and lower GFAP levels than ICH patients. The best biomarker combination for the identification of IS was RBP-4+NT-proBNP, which was able to identify 29.7% of IS patients with 100% specificity. In the subset of patients for whom GFAP was measured with the high-sensitivity assay, RBP-4, NT-proBNP and GFAP identified 51.5% of IS patients with 100% specificity. When stroke mimics were included, specificities were reduced to 98.4 and 96.8%, respectively. POCTs of RBP-4 and NT-proBNP showed results similar results to those of conventional ELISAs.Conclusions:A biomarker panel including RBP-4, NT-proBNP and GFAP provided moderate but potentially useful sensitivity rates at 100% specificity for IS diagnosis. If confirmed in future studies, this strategy might allow pre-hospital treatment in selected patients.Classification of Evidence:This study provides Class I evidence that a biomarker panel including RBP-4, NT-proBNP and GFAP distinguishes IS from ICH with moderate accuracy.==========