Department of Anatomy, ELKH-PTE PACAP Research Team, Centre for Neuroscience, Medical School, University of Pécs, 7624 Pécs, Hungary.
1st Department of Medicine, Division of Hematology, Medical School, University of Pécs, 7624 Pécs, Hungary.
Int J Mol Sci. 2023 Jun 28;24(13):10801. doi: 10.3390/ijms241310801.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide with well-known anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects. PACAP regulates the production of various proinflammatory factors and may influence the complex cytokine network of the bone marrow microenvironment altered by plasma cells, affecting the progression of multiple myeloma (MM) and the development of end-organ damage. The aim of our study was to investigate the changes in PACAP-38 levels in patients with MM to explore its value as a potential biomarker in this disease. We compared the plasma PACAP-38 levels of MM patients with healthy individuals by ELISA method and examined its relationship with various MM-related clinical and laboratory parameters. Lower PACAP-38 levels were measured in MM patients compared with the healthy controls, however, this difference vanished if the patient achieved any response better than partial response. In addition, lower peptide levels were found in elderly patients. Significantly higher PACAP-38 levels were seen in patients with lower stage, lower plasma cell infiltration in bone marrow, lower markers of tumor burden in serum, lower total urinary and Bence-Jones protein levels, and in patients after lenalidomide therapy. Higher PACAP-38 levels in newly diagnosed MM patients predicted longer survival and a higher probability of complete response to treatment. Our findings confirm the hypothesis that PACAP plays an important role in the pathomechanism of MM. Furthermore, our results suggest that PACAP might be used as a valuable, non-invasive, complementary biomarker in diagnosis, and may be utilized for prognosis prediction and response monitoring.
垂体腺苷酸环化酶激活肽（PACAP）是一种具有多种功能的神经肽，具有众所周知的抗炎、抗氧化、抗肿瘤和免疫调节作用。PACAP 调节各种促炎因子的产生，并可能影响浆细胞改变的骨髓微环境的复杂细胞因子网络，影响多发性骨髓瘤（MM）的进展和终末器官损伤的发展。我们的研究目的是探讨 MM 患者 PACAP-38 水平的变化，以探索其作为该疾病潜在生物标志物的价值。我们通过 ELISA 方法比较了 MM 患者和健康个体的血浆 PACAP-38 水平，并检查了其与各种 MM 相关的临床和实验室参数的关系。与健康对照组相比，MM 患者的血浆 PACAP-38 水平较低，但如果患者达到任何优于部分缓解的反应，这种差异就会消失。此外，老年患者的肽水平较低。在分期较低、骨髓浆细胞浸润程度较低、血清肿瘤负荷标志物较低、总尿和 Bence-Jones 蛋白水平较低以及接受来那度胺治疗的患者中，PACAP-38 水平明显升高。新诊断的 MM 患者中较高的 PACAP-38 水平预示着更长的生存时间和更高的完全缓解治疗概率。我们的发现证实了 PACAP 在 MM 发病机制中起重要作用的假设。此外，我们的结果表明，PACAP 可能作为一种有价值的、非侵入性的、补充性生物标志物用于诊断，并可能用于预后预测和反应监测。
