Dowling Paul, Hayes Catriona, Ting Kay Reen, Hameed Abdul, Meiller Justine, Mitsiades Constantine, Anderson Kenneth C, Clynes Martin, Clarke Colin, Richardson Paul, O'Gorman Peter
Department of Biology, National University of Ireland, Maynooth, Co, Kildare, Ireland.
BMC Genomics. 2014 Oct 17;15(1):904. doi: 10.1186/1471-2164-15-904.
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.
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.
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.
骨质破坏是多发性骨髓瘤的一个特征，其特点是由于破骨细胞活性增加和成骨细胞活性受到抑制或缺失而导致溶骨性骨质破坏。几乎所有多发性骨髓瘤患者都会出现溶骨性骨病变，伴有严重且使人衰弱的骨痛、病理性骨折、高钙血症和脊髓压迫，以及死亡率增加。骨重塑生物标志物用于识别有助于选择患者最佳治疗方案的疾病特征。然而，需要更准确的生物标志物来有效反映骨病活动的动态变化。
采用基于无标记质谱的策略对与无骨病或高骨病相关的分级患者血清样本进行发现阶段分析。鉴定出了许多与骨病在统计学上显著相关的蛋白质，包括酶、细胞外基质糖蛋白和补体系统成分。
补体C4和血清对氧磷酶/芳基酯酶1的酶联免疫吸附测定表明，在一个更大的独立患者样本队列中，这些蛋白质与高骨病相关。因此，这些生物分子在评估骨病程度方面可能具有临床应用价值。
