Induction of systemic disease-specific salivary biomarker profiles in mouse cancer models

Saliva (oral fluids) is an emerging biofluid poised for clinical diseases detection. Although the rationale for oral diseases applications (e.g. oral cancer) is clear, the rationale and relationship between systemic diseases and saliva biomarkers are unknown. In this study, we used mouse models of melanoma and non-small cell lung cancer and compared the transcriptome biomarker profiles of tumor-bearing mice to those of control mice. Microarray analysis showed that salivary transcriptomes were significantly altered in tumor-bearing mice vs. controls. Analysis of the transcriptomes in the mouse tumors, serum, salivary glands and saliva revealed that salivary biomarkers have multiple origins. Furthermore, we identified that the expression of two groups of significantly altered transcription factors Runx1, Mlxipl, Trim30 and Egr1, Tbx1, Nr1d1 in melanoma-bearing mice that can potentially be responsible for 82.6% of the up-regulated genes expression and 62.5% of the down-regulated gene expression in the mice saliva, respectively. We also confirmed that the ectopic production of nerve growth factor (NGF) in the melanoma tumor tissue as a tumor-released mediator that can induce expression of the transcription factor Egr-1 in the salivary gland. Taken together, our data support the conclusion that upon systemic disease development, a disease-specific change occurs in the salivary biomarker profile. Although the origins of the disease-specific salivary biomarkers are both systemic and local, stimulation of salivary gland by mediators released from remote tumors play an important role in regulating the salivary surrogate biomarker profiles.

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Gao K, Zhou H, Zhang L, Lee JW, Zhou Q, Hu S, Wolinsky LE, Farrell J, Eibl G, Wong DT