Background The bone marrow microenvironment provides an optimal substrate for multiple myeloma (MM) initiation and progression. The soluble component of MM niche is dynamic with the disease states of MM. We formerly employed proteomic profiling to construct a MM model. Four peptides constituting the model were selected by supervised neural network algorithm (SNN). Methods 62 Newly diagnosed (ND) MM and 64 healthy controls (HCs) were picked up for validating the distinguishing capability of the SNN model. Nano-liquid chromatography-electrospray ionization-tandem mass spectrometry was used for peptide identification. MM in different disease states and HCs were choosed for peptides relative intensities comparison. Western blot and ELISA were employed to validate the variability. Results The sensitivity and specificity of the independent testing data set for blind validation were 93.55% and 92.19%. The relative intensities of three out of the four peptides were increased in ND and refractory and relapse patients but decreased to that level of HCs in complete remission and very good partial remission patients. Relative intensity of the remaining peptide was negatively associated with MM remission. The peptides sequencing results showed that they were derived from dihydropyrimidinase-like 2, fibrinogen alpha chain, platelet factor 4 and alpha-fetoprotein. Conclusions The potential value of the four peptides in monitoring MM treatment response was arised from their close correlation with MM disease states.

中文翻译：

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血清新型血清肽生物标志物的变异性与多发性骨髓瘤的疾病状态相关。

背景 骨髓微环境为多发性骨髓瘤 (MM) 的发生和发展提供了最佳基质。MM 生态位的可溶性成分与 MM 的疾病状态是动态的。我们以前使用蛋白质组学分析来构建 MM 模型。通过监督神经网络算法（SNN）选择构成模型的四种肽。方法选取62例新诊断（ND）MM和64例健康对照（HC），验证SNN模型的区分能力。纳米液相色谱-电喷雾电离-串联质谱用于肽鉴定。选择不同疾病状态的MM和HCs进行肽相对强度比较。使用蛋白质印迹和ELISA来验证变异性。结果盲验证的独立测试数据集的敏感性和特异性分别为93.55%和92.19%。四种肽中三种的相对强度在 ND 和难治性和复发患者中增加，但在完全缓解和非常好的部分缓解患者中降低到 HCs 的水平。剩余肽的相对强度与 MM 缓解呈负相关。多肽测序结果表明它们来源于二氢嘧啶酶样2、纤维蛋白原α链、血小板因子4和甲胎蛋白。结论 四种肽在监测 MM 治疗反应中的潜在价值源于它们与 MM 疾病状态的密切相关性。四种肽中三种的相对强度在 ND 和难治性和复发患者中增加，但在完全缓解和非常好的部分缓解患者中降低到 HCs 的水平。剩余肽的相对强度与 MM 缓解呈负相关。多肽测序结果表明它们来源于二氢嘧啶酶样2、纤维蛋白原α链、血小板因子4和甲胎蛋白。结论 四种肽在监测 MM 治疗反应中的潜在价值源于它们与 MM 疾病状态的密切相关性。四种肽中三种的相对强度在 ND 和难治性和复发患者中增加，但在完全缓解和非常好的部分缓解患者中降低到 HCs 的水平。剩余肽的相对强度与 MM 缓解呈负相关。多肽测序结果表明它们来源于二氢嘧啶酶样2、纤维蛋白原α链、血小板因子4和甲胎蛋白。结论 四种肽在监测 MM 治疗反应中的潜在价值源于它们与 MM 疾病状态的密切相关性。多肽测序结果表明它们来源于二氢嘧啶酶样2、纤维蛋白原α链、血小板因子4和甲胎蛋白。结论 四种肽在监测 MM 治疗反应中的潜在价值源于它们与 MM 疾病状态的密切相关性。多肽测序结果表明它们来源于二氢嘧啶酶样2、纤维蛋白原α链、血小板因子4和甲胎蛋白。结论 四种肽在监测 MM 治疗反应中的潜在价值源于它们与 MM 疾病状态的密切相关性。