Systemic Disease-Induced Salivary Biomarker Profiles in Mouse Models of Melanoma and Non-Small Cell Lung Cancer

Abstract

BackgroundSaliva (oral fluids) is an emerging biofluid poised for detection of clinical diseases. Although the rationale for oral diseases applications (e.g. oral cancer) is intuitive, the rationale and relationship between systemic diseases and saliva biomarkers are unclear.Methodology/Principal FindingsIn 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. Significant overlapping among transcriptomes of mouse tumors, serum, salivary glands and saliva suggests that salivary biomarkers have multiple origins. Furthermore, we identified that the expression of two groups of significantly altered transcription factors (TFs) Runx1, Mlxipl, Trim30 and Egr1, Tbx1, Nr1d1 in salivary gland tissue of melanoma-bearing mice can potentially be responsible for 82.6% of the up-regulated gene expression and 62.5% of the down-regulated gene expression, respectively, in the saliva of melanoma-bearing mice. We also showed that the ectopic production of nerve growth factor (NGF) in the melanoma tumor tissue as a tumor-released mediator can induce expression of the TF Egr-1 in the salivary gland.ConclusionsTaken together, our data support the conclusion that upon systemic disease development, significant changes can occur in the salivary biomarker profile. Although the origins of the disease-induced salivary biomarkers may be both systemic and local, stimulation of salivary gland by mediators released from remote tumors plays an important role in regulating the salivary surrogate biomarker profiles.

Prostatic acid phosphatase is the main acid phosphatase with 5′-ectonucleotidase activity in the male mouse saliva and regulates salivation

“…Moreover, we did not observe differences in the total protein concentration or ␣-amylase activity between wild-type and PAP Ϫ/Ϫ mice. However, we cannot disregard potential differences in the particular composition of the saliva, considering that systemic diseases can induce alterations in the profile of components that are secreted into the saliva (15,30).…”

Role of Pancreatic Cancer-derived Exosomes in Salivary Biomarker Development

“…Collection of Mouse Saliva, Blood, and Tumor Tissue-Saliva, blood, and tumor tissue from mice were collected as described previously (26). Upon the development of the pancreatic tumor (4 weeks), saliva was collected, and then the mouse was sacrificed.…”

Salivary microRNAs Show Potential as a Noninvasive Biomarker for Detecting Resectable Pancreatic Cancer

“…First, miRNAs in tissue, plasma, and saliva from the same patient were not profiled at the same time, and therefore miRNA profiles of tissue, plasma, and saliva could not be compared. Although previous studies showed that salivary mRNA profiles did not overlap with those of tissue or serum (37), the occurrence of this phenomenon for miRNA profiles needs to be explored. Second, reagents and technologies to detect Lewis blood group antigens are not yet readily available in China, so the Lewis blood groups of the subjects could not be determined to assess whether these blood antigens influence salivary miRNAs expression as they do serum CA19-9 expression.…”