Identification of proteins found to be significantly altered when comparing the serum proteome from Multiple Myeloma patients with varying degrees of bone disease

Abstract

Background: Bone destruction is a feature of multiple myeloma, characterised by osteolytic bone destruction due to increased osteoclast activity and suppressed or absent osteoblast activity. Almost all multiple myeloma patients develop osteolytic bone lesions associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Biomarkers of bone remodelling are used to identify disease characteristics that can help select the optimal management of patients. However, more accurate biomarkers are needed to effectively mirror the dynamics of bone disease activity.

Results: A label-free mass spectrometry-based strategy was employed for discovery phase analysis of fractionated patient serum samples associated with no or high bone disease. A number of proteins were identified which were statistically significantly correlated with bone disease, including enzymes, extracellular matrix glycoproteins, and components of the complement system.

Conclusions: Enzyme-linked immunosorbent assay of complement C4 and serum paraoxonase/arylesterase 1 indicated that these proteins were associated with high bone disease in a larger independent cohort of patient samples. These biomolecules may therefore be clinically useful in assessing the extent of bone disease.

Figure 1

STRING analysis of 24 differentially expressed proteins listed in Table 2 . The STRING program generates functional protein association networks. (A) Evidence view; uses different-coloured lines to depict the type of evidence that supports each interaction. (B) Action view; uses different-coloured lines to depict the types of interaction between proteins.

Figure 2

Box and whisker plots and ROC curves with associated AUC-values for Complement C4 (A) and PON1 - Serum paraoxonase/arylesterase (B) in patient samples (Pre-malignant Myeloma: MGUS/SMM, MM: No Bone Disease and MM: High Bone Disease). The box and whisker plots display information on the range, median and quartiles. A total of 31 patient samples with no bone disease, 39 patient samples with high bone disease and 21 patient samples with MGUS/SMM were screened by ELISA.