Saliva proteomic analysis reveals possible biomarkers of renal cell carcinoma

Early diagnosis is a key to improve the prognosis of renal cell carcinoma (RCC); however, reliable RCC biomarkers are lacking in clinical practice. In this study, we used isobaric tags for relative and absolute quantification-based mass spectrometry to identify salivary proteins as biomarkers for the diagnosis of RCC. The objective of this study is to discover biomarkers from saliva by utilizing high-throughput quantitative proteomics approaches. Saliva proteins from 124 RCC patients and healthy individuals were identified and quantified. RCC putative biomarkers were verified by real-time polymerase chain reaction or enzyme-linked immunosorbent assay in a prevalidation sample set. Seventy-one differentially expressed salivary proteins were identified. Serotransferrin, haptoglobin, KRT9, and S100A9, which in previous studies were found to be most closely related to cancers, were selected as putative RCC biomarkers. Haptoglobin and S100A9 were significantly elevated in RCC compared with healthy control samples, although the expression of serotransferrin and KRT9 did not differ between the groups. Furthermore, receiver operating characteristic curves with a cut-off value of 75.49 ng/mL for S100A9 revealed a sensitivity of 87.10% and a specificity of 91.94% for discriminating RCC patients from healthy individuals. Salivary haptoglobin differentiated RCC patients from healthy controls with a sensitivity of 85.48% and specificity of 80.65% (cut-off value 43.02 µg/mL). These results provide experimental evidence to support S100A9 and haptoglobin as potential novel, noninvasive biomarkers for the diagnosis of RCC.