High Expression of Phosphorylated Extracellular Signal-Regulated Kinase (ERK1/2) is Associated with Poor Prognosis in Newly Diagnosed Patients with Multiple Myeloma

BACKGROUND: Previous research has demonstrated that the extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway is commonly activated in multiple myeloma (MM) patients. However, the prognostic value of activation of the MEK/ERK signaling pathway in newly diagnosed patients with MM has not been reported. MATERIAL/METHODS: Expression levels of p-ERK1/2 protein in bone marrow biopsy specimens obtained from 60 newly diagnosed patients with MM were analyzed using immunohistochemistry, and classified into 3 groups: high p-ERK1/2 expression, low p-ERK1/2 expression, and negative group. Correlations between clinicopathological characteristics, including expression levels of p-ERK1/2 protein, progression-free survival (PFS), and overall survival (OS), were analyzed using univariate and multivariate analysis. RESULTS: Phosphorylated-ERK1/2 protein was positive in 47 bone marrow specimens, including 19 specimens with high p-ERK1/2 expression and 28 specimens with low p-ERK1/2 expression. Univariate Kaplan-Meier analysis showed that in newly diagnosed patients with MM, high p-ERK1/2 expression, high ISS staging, serum creatinine (Scr) ≥177 μmol/l, serum β(2)-microglobulin (β(2)-MG) ≥5.5 μmol/l, and serum calcium (Ca) ≥2.75 mmol/l were significantly associated with shorter OS and PFS. Additionally, high ECOG scores (score 2–4) were associated with shorter PFS in newly diagnosed patients with MM. Multivariate Cox regression analysis showed that in newly diagnosed patients with MM, high p-ERK1/2 expression was significantly associated with shorter OS and PFS. Additionally, in newly diagnosed patients with MM, serum Ca ≥2.75 mmol/l was significantly associated with shorter PFS, and serum β(2)-MG ≥5.5 μmol/l was significantly associated with shorter OS. CONCLUSIONS: High p-ERK1/2 expression is an independent factor for poor prognosis in newly diagnosed patients with MM.