Assessment of the serum level of Endothelin-1 in patients with multiple myeloma

Abstract

Background
Multiple myeloma (MM) is the second most common hematological malignancy, and accounts for 10% of all hematological malignancies. Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor, mainly secreted by endothelial cells. In addition to its role as a potent endogenous vasoconstrictor and mediator of cardiovascular and renal disorders, the endothelin axis has emerged as an important player in tumor growth and metastasis by regulating cell survival, angiogenesis, invasion, and metastatic dissemination. The activation of ET-1 axis has been shown to contribute to MM cells survival, immune-evasion, angiogenesis, and drug resistance.


Patients and methods
This study is an exploratory case-control study that included 45 patients with MM, recruited at the Clinical Hematology, Oncology and Bone Marrow Transplantation Department, Internal Medicine Department, Ain Shams University Hospitals, both in an inpatient and outpatient setting. The study period was one year from May 2022 to May 2023. It included 15 Patients with newly diagnosed MM before receiving any treatment, 15 Patients with MM who have received three cycles of chemotherapy and are in remission (including complete remission and partial remission), and 15 Patients who were refractory to treatment (progressive disease) according to the International Myeloma working group response criteria. The study also included 30 healthy control patients.


Results
ET-1 levels were significantly elevated in MM patients, compared with healthy control subjects. ET-1 levels were highest in newly diagnosed patients (198 ng/l), followed by those resistant to treatment (188 ng/l), and lowest in patients in remission (69 ng/l).
ET-1 levels correlated with disease stage; patients with advanced disease (stage 3) had higher ET-1 levels than those with early-stage disease (stage 1).
ET-1 levels were lower in patients in remission compared with those with refractory disease. This suggests a potential association between ET-1 levels and treatment response.


Conclusion
Our findings demonstrate that elevated ET-1 levels are associated with disease severity and poor prognosis in multiple myeloma patients. Specifically, higher ET-1 levels were observed in newly diagnosed patients and those resistant to treatment, suggesting a potential role in disease progression. Conversely, lower ET-1 levels were associated with better treatment response in patients in remission. These results suggest that ET-1 could serve as a valuable biomarker for disease activity and prognosis. Furthermore, targeting the ET-1 pathway may represent a promising therapeutic strategy for MM.