Proteomic Alterations in Multiple Myeloma: A Comprehensive Study Using Bone Marrow Interstitial Fluid and Serum Samples

Multiple myeloma (MM) is a plasma cell associated cancer and the second most common hematological malignancies. Although researchers have been working on MM, comprehensive quantitative proteomic analysis of Bone Marrow Interstitial Fluid (BMIF) and Blood Serum is not yet reported. Being a proximal biofluid for the hematological malignancies, BMIF could serve as a potential source for identifying diagnostic, prognostic and therapeutic markers for various blood cancers including MM. Moreover, serum, being a minimal invasive biofluid, serves as a potential source for discovering diagnostic and prognostic markers for various cancers including MM as well. We employed multipronged quantitative proteomic approaches like iTRAQ and SWATH-MS for MM BMIF and serum where we identified 279 and 116 non-redundant differentially expressed proteins in MM BMIF and serum respectively. Additionally, the probable biological and functional roles of the differentially abundant proteins were probed in the manifestation of MM disease pathology by using various bioinformatic tools. Furthermore, a selected panel of statistically significant proteins was verified for their differential abundance by immunoblotting as well as MS-based SRM assays. The significant discrimination efficiency of the models generated through multivariate statistical analysis was decent to distinguish between the MM and controls. Moreover, potential candidate proteins were also validated in a fresh independent cohort of serum samples using Enzyme-linked immunosorbent assay (ELISA), as it is a minimal invasive fluid that could easily be used for the diagnostics applications. The significance of this study remains in the fact that the proteins which are observed in the BMIF and also reflected in the serum with similar expression profile are proposed as a potential candidate biomarker panel for MM diagnosis.