Salivary proteins from dysplastic leukoplakia and oral squamous cell carcinoma and their potential for early detection.

Dysplastic leukoplakia (LP) of the oral cavity is a potentially malignant condition for oral squamous cell carcinoma (OSCC), early detection of which remains an unmet clinical need. In an effort to develop non-invasive biomarker based method for early detection of the disease, differential proteomic profiling was carried out with the saliva from patients with risk habits and diagnosed with LP and those with lymph node negative and positive OSCC in comparison to healthy controls with risk habits. Ninety three proteins were observed at elevated level (≥1.5 fold), and 30 were prioritized based on a scoring system comprising of confidence of identification, presence in the various specimen groups, functional relevance, and their secretory potential. Verification was carried out in independent patient cohorts for 8 selected, representative, upregulated proteins using ELISA. Three of them CD44, S100A7, and S100P were significantly altered in patients with LP as well as OSCC and can be regarded as a panel of biomarker candidates for early detection of the malignancy. Other members may also be investigated in a targeted manner to expand the portfolio of biomarkers for early detection. The mass spectrometry data are available via ProteomeXchange with identifier PXD015722. SIGNIFICANCE: There is an unmet clinical need for non-invasive, biomarker based methods for the improved early detection and the subsequent management of oral cancer. The study represents differential proteome profiling of the saliva of patients with oral dysplastic leukoplakia (LP) - a potentially malignant lesion, patients diagnosed with oral squamous cell carcinoma (OSCC), and healthy controls to identify potential markers for the purpose of early detection of malignancy. From among the matched and prioritized proteins with elevated levels in the saliva of patients with LP and those with OSCC, eight were verified. Three of them - CD44, S100A7 and S100P appeared promising candidates as biomarkers for early detection of the neoplastic predisposition and may form the basis of clinical assays for this purpose.

Data from human salivary proteome - A resource of potential biomarkers for oral cancer.

Salivary proteins are an important source for developing marker-based assays for oral cancers. To get an insight into the proteins present in human saliva, we applied multiple strategies involving affinity-based depletion of abundant proteins, fractionation of the resulting proteins or their tryptic peptides followed by LC-MS/MS analysis, using high resolution mass spectrometry. By integrating the protein identifications observed by us with those from similar workflows employed in earlier investigations, we compiled an updated salivary proteome. We have mapped the salivary proteome to the published data on differentially expressed proteins from oral cancer tissues and also for their secretory features using prediction tools, SignalP 4.1, TMHMM 2c and Exocarta. Proteotypic peptides for the subset of proteins implicated in oral cancer and mapped to any two of the prediction tools for secretory potential have been listed. The data here are related to the research article "Human saliva proteome - a resource of potential biomarkers for oral cancer" in the Journal of Proteomics [1].

Human salivary proteome--a resource of potential biomarkers for oral cancer.

Proteins present in human saliva offer an immense potential for clinical applications. However, exploring salivary proteome is technically challenged due to the presence of amylase and albumin in high abundance. In this study, we used four workflows to analyze human saliva from healthy individuals which involved depletion of abundant proteins using affinity-based separation methods followed by protein or peptide fractionation and high resolution mass spectrometry analysis. We identified a total of 1256 human salivary proteins, 292 of them being reported for the first time. All identifications were verified for any shared proteins/peptides from the salivary microbiome that may conflict with the human protein identifications. On integration of our results with the analyses reported earlier, we arrived at an updated human salivary proteome containing 3449 proteins, 808 of them have been reported as differentially expressed proteins in oral cancer tissues. The secretory nature of 598 of the 808 proteins has also been supported on the basis of the presence of signal sequence, transmembrane domain or association with exosomes. From this subset, we provide a priority list of 139 proteins along with their proteotypic peptides, which may serve as a reference for targeted investigations as secretory markers for clinical applications in oral malignancies. This article is part of a Special Issue entitled: Proteomics in India.