Abstract
Objective: The objective of this study was to determine if protein-by-products secondary to cervical cancer oncogenes appear in the saliva.Methods: Four pooled (n=10 subjects/pool) stimulated whole saliva specimens from women were analyzed. One pooled specimen was from healthy women, while other pooled specimens were from women diagnosed with CIN 2 moderate cervical dysplasia (n=10), CIN 3 severe cervical dysplasia (n=10) and the other pooled group from women diagnosed with cervical carcinoma in situ (n=10). Differential expression of proteins was measured by isotopically tagging proteins in each groups and comparing them to the healthy control group. Saliva from each of the pooled samples was trypsinized and the peptide digests labeled with the appropriate iTRAQ reagent. Labeled peptides from each of the digests were combined and analyzed by reverse phase (C18) capillary chromatography on an Applied Biosystems QStar LC-MS/MS mass spectrometer equipped with an LC-Packings HPLC.Results: The results of the salivary analyses yielded approximately 133 proteins in the saliva specimens. Forty eight proteins were differentially expressed between the healthy control pool, precancerous and cancerous conditions.Conclusions: The study suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be modulated secondary to precancerous and cancerous conditions and that these proteins may be useful in the study of cervical cancer progression, treatment efficacy and the tailoring of individualized patient care.
Highlights
Invasive cervical cancer is the second most common cause of death from cancer among women (Bosch et al, 1995)
Forty eight proteins were differentially expressed between the healthy control pool, precancerous and cancerous conditions
The study suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be modulated secondary to precancerous and cancerous conditions and that these proteins may be useful in the study of cervical cancer progression, treatment efficacy and the tailoring of individualized patient care
Summary
Invasive cervical cancer is the second most common cause of death from cancer among women (Bosch et al, 1995). The number of deaths was 2.3 per 100,000 women per year. These rates are age-adjusted and based on 2008-2012 cases and deaths as reported by the NCI Surveillance, 2014, Epidemiology and End Results Program. Cervical lesions are divided into different stages of aberrant cell growth. The initial stages are the precancerous conditions designated as cervical intraepithelial neoplasia (CIN) which exhibit alteration of the cervical epithelial lining with the presence of abnormal cell growth (Garbett et al, 2014). CIN status is determined by the extent in which the cervical epithelial lining and is divided into three stages based on the histological features, nuclear changes and the extent of epithelial involvement. The grades are mild, moderate and severe with the moderate and severe conditions having a higher likelihood to progress into carcinoma in situ (CIS) or invasive carcinoma (Garbett et al, 2014)
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