Saliva proteomic analysis reveals possible biomarkers of renal cell carcinoma

Abstract

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.

Haptoglobin as a biomarker

“…Следует также отметить возможность использования не только плазмы, но и слюны для детекции онкомаркеров [98], и Hp в том числе [99]. Например, сравнительный протеомный анализ выявил достоверное превышение (в 2,5 раза) уровня Hp в слюне у пациентов с раком почки по сравнению со здоровыми донорами [99].…”

“…Следует также отметить возможность использования не только плазмы, но и слюны для детекции онкомаркеров [98], и Hp в том числе [99]. Например, сравнительный протеомный анализ выявил достоверное превышение (в 2,5 раза) уровня Hp в слюне у пациентов с раком почки по сравнению со здоровыми донорами [99]. Авторы этого исследования делают вывод о том, что их экспериментальные результаты указывают на возможность использования гаптоглобина наряду с белком S100A9 в качестве потенциальных неинвазивных биомаркеров для диагностики рака почки.…”

Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas

“…Saliva is one of the complex and important multi-constituent body fluids that reflects a wide variety of physiological knowledge due to its contents extensively supplied by the blood. Moreover, a saliva-based diagnosis has been drawing attention in the diagnosis of systemic diseases such as renal cancers, due to the source, composition, function, and interaction of saliva with the substances that make up the plasma [ 29 , 30 ]. In the present study, besides blood components and urine, we also demonstrated the potential of saliva as a non-invasive potential media for RCC diagnosis, especially in chRCC.…”

Haptoglobin as a Biomarker

“…It should also be noted that it is possible to use not only plasma but also saliva for the detection of tumor markers [ 98 ], including haptoglobin [ 99 ]. For example, comparative proteomic analysis revealed a significant excess (2.5 times) of the level of haptoglobin in saliva in patients with kidney cancer compared with healthy donors [ 99 ].…”

“…It should also be noted that it is possible to use not only plasma but also saliva for the detection of tumor markers [ 98 ], including haptoglobin [ 99 ]. For example, comparative proteomic analysis revealed a significant excess (2.5 times) of the level of haptoglobin in saliva in patients with kidney cancer compared with healthy donors [ 99 ]. The authors of this study conclude that their experimental results indicate the possibility of using haptoglobin along with the S100A9 protein as potential non-invasive biomarkers for the diagnosis of kidney cancer.…”