Mielnik Michał, Szudy-Szczyrek Aneta, Homa-Mlak Iwona, Mlak Radosław, Podgajna-Mielnik Martyna, Gorący Aneta, Małecka-Massalska Teresa, Hus Marek
Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland.
Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland.
Biomedicines. 2023 Nov 9;11(11):3012. doi: 10.3390/biomedicines11113012.
Multiple myeloma (MM) is the second most common hematological neoplasm. Cytokines, chemokines, and their receptors, induced by the microenvironment of MM, participate in tumor growth, the attraction of leukocytes, cell homing, and bone destruction. This study aimed to assess the correlation between the pretreatment serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), angiogenic chemokine monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) and the clinical outcomes and survival of patients newly diagnosed with MM. The study group consisted of 82 individuals. The IL-8 concentration was significantly positively correlated with the age of onset ( = 0.007), the International Staging System (ISS) stage ( = 0.03), the Eastern Cooperative Oncology Group (ECOG) performance status ( < 0.001), the degree of anemia before treatment ( < 0.0001), the degree of kidney disease ( < 0.001), and VEGF ( = 0.0364). Chemotherapy responders had significantly lower concentrations of IL-8 ( < 0.001), IL-6 ( < 0.001), and VEGF ( = 0.04) compared with non-responders. Patients with treatment-induced polyneuropathy had significantly higher levels of IL-8 ( = 0.033). Patients with a high level of IL-6 had a 2-fold higher risk of progression-free survival (PFS) reduction (17 vs. 35 months; HR = 1.89; = 0.0078), and a more than 2.5-fold higher risk of overall survival (OS) reduction (28 vs. 78 months; HR = 2.62; < 0.001). High levels of IL-6, IL-8, and VEGF demonstrated significant predictive values for some clinical conditions or outcomes of newly diagnosed MM patients. Patients with an early response to chemotherapy had a significantly lower concentration of these cytokines. A high pretreatment IL-6 concentration was an independent negative prognostic marker for newly diagnosed MM patients.
多发性骨髓瘤(MM)是第二常见的血液系统肿瘤。由MM微环境诱导产生的细胞因子、趋化因子及其受体参与肿瘤生长、白细胞吸引、细胞归巢和骨质破坏。本研究旨在评估白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、血管生成趋化因子单核细胞趋化蛋白-1(MCP-1)和血管内皮生长因子(VEGF)的预处理血清浓度与新诊断MM患者的临床结局及生存情况之间的相关性。研究组由82名个体组成。IL-8浓度与发病年龄(P = 0.007)、国际分期系统(ISS)分期(P = 0.03)、东部肿瘤协作组(ECOG)体能状态(P < 0.001)、治疗前贫血程度(P < 0.0001)、肾脏疾病程度(P < 0.001)以及VEGF(P = 0.0364)显著正相关。与无反应者相比,化疗有反应者的IL-8(P < 0.001)、IL-6(P < 0.001)和VEGF(P = 0.04)浓度显著更低。发生治疗诱导性多发性神经病的患者IL-8水平显著更高(P = 0.033)。IL-6水平高的患者无进展生存期(PFS)缩短风险高2倍(17个月对35个月;风险比[HR] = 1.89;P = 0.0078),总生存期(OS)缩短风险高2.5倍以上(28个月对78个月;HR = 2.62;P < 0.001)。高水平的IL-6、IL-8和VEGF对新诊断MM患者的某些临床情况或结局具有显著预测价值。化疗早期有反应的患者这些细胞因子浓度显著更低。预处理时IL-6浓度高是新诊断MM患者的独立不良预后标志物。