Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America.
PLoS One. 2013;8(3):e58504. doi: 10.1371/journal.pone.0058504. Epub 2013 Mar 27.
Multiple myeloma (MM) is an incurable bone marrow malignancy of the B cell lineage. Utilizing multiplex Luminex technology we measured levels of 25 cytokines in the plasma of normal donors (n = 177), those with monoclonal gammopathy of undetermined significance (n = 8), and MM patients (n = 55) with either active disease, on treatment, or in remission. The cytokine levels were compared between normal donors and MM patients as well as between various phases of MM, and discriminant analysis was used to create a predictive classification model based on the differentially expressed cytokines. Evaluating age- and gender-dependence of cytokine expression, we determined that with age there is a shift toward a pro-inflammatory environment. Moreover, we observed a strong gender bias in cytokine expression. However, the profile of differentially expressed cytokines was heavily skewed toward an anti-inflammatory, pro-tumorigenic response in patients with MM. Significantly, our predictive model placed all patients in remission in the same category as those with active disease. Thus, our study demonstrates that the homeostasis of systemic cytokines is not restored when MM patients enter remission, suggesting that once an individual has cancer, the microenvironment is permanently altered and the system is primed for a relapse.
多发性骨髓瘤（MM）是一种不可治愈的骨髓恶性肿瘤，属于 B 细胞系。我们利用多重 Luminex 技术测量了正常供体（n=177）、意义未明单克隆丙种球蛋白血症（n=8）和多发性骨髓瘤患者（n=55）的血浆中 25 种细胞因子的水平，这些患者的疾病处于活动期、治疗中或缓解期。我们比较了正常供体和 MM 患者之间以及 MM 各个阶段之间的细胞因子水平，并利用判别分析基于差异表达的细胞因子创建了一个预测分类模型。评估细胞因子表达的年龄和性别依赖性，我们发现随着年龄的增长，环境向促炎方向转变。此外，我们观察到细胞因子表达存在强烈的性别偏见。然而，在 MM 患者中，差异表达细胞因子的特征严重偏向抗炎、促肿瘤反应。重要的是，我们的预测模型将所有缓解期患者与活动期患者归为同一类别。因此，我们的研究表明，当 MM 患者进入缓解期时，全身细胞因子的平衡并未恢复，这表明一旦个体患有癌症，微环境就会永久改变，系统就会为复发做好准备。
