Saliva-Omics in Plasma Cell Disorders — Proof of Concept and Potential As a Non-Invasive Tool for Monitoring Disease Burden and MRD Status

Salivaomics has exciting potential for the diagnosis and monitoring of malignancy, evidence of which has been reported in oral cancer (Sahibzada et al., 2017), head and neck malignancies (Citrin et al., 2012) and ovarian cancer (Chen et al., 1990). It has been observed that approximately 40% of cancer, stroke and cardiovascular disease biomarkers are present in whole saliva (Loo et al., 2010). Salivaomics has become an area of great interest in disease diagnosis over the last number of years, following the footsteps of the other “omics” based diagnostic tools. Saliva has been referred to as “the mirror of the body” as it gives an insight into the internal pathological state (Lee and Wong, 2009). As saliva is considered a fast, inexpensive and non-invasive method of sample collection, the future of diagnosis, early detection, monitoring and prediction of progression of disease has been thought to lie here. Monoclonal gammopathy of undetermined significance (MGUS) is characterised as a premalignant precursor tumours of MM. It has been seen that the majority of MM cases develop from MGUS (Weiss et al., 2009), leading to the need for biomarkers to monitor disease progression and explore the mechanism of malignant transformation. Serum and saliva samples were collected from 18 newly diagnosed MM patients and 8 MGUS patients, peptides were purified using the filter aided sample preparation (FASP) method and samples were prepared for label-free liquid chromatography mass spectrometry (LC-MS/MS) using an LTQ Orbitrap XL mass spectrometrer (Thermo Fisher Scientific). Proteins were analysed using the MaxQuant and Perseus software for mass-spectrometry (MS)-based proteomics data analysis, UniProtKB-Swiss Prot database and KEGG Pathway database. The abundance of proteins in saliva from MGUS compared to newly diagnosed MM was analysed using label-free mass spectrometry. A panel of 6 significant proteins was identified. Fatty Acid Binding Protein 5 (FABP5) was detected in elevated levels in saliva from MM patients compared to MGUS. The increased expression was verified using western blotting. Fatty Acid Binding Protein 5 (FABP5) is known to promote cell proliferation, survival and migration (Wang et al., 2006). FABP5 has been observed to aid in the proliferation of cancer and has been seen to be overexpressed in multiple cancer types such as breast (Levi et al., 2013), prostate (Morgan et al., 2008) and HCC (Ohata et al., 2017). FABP5 has seen to link closely with poor