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30 May 2017 : Clinical Research

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

Liping Fan1ABCDEF, Jinquan Hong2CF, Haobo Huang1ABCDEFG*, Danhui Fu13ACDE, Shunquan Wu3BCF, Qingqing Wang3BC, Yamei Ye3BC, Yun Liu3B

DOI: 10.12659/MSM.901850

Med Sci Monit 2017; 23:2636-2643

Abstract

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 AND 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 β2-microglobulin (β2-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 β2-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.

Keywords: Biopsy, Bone Marrow, MAP Kinase Signaling System, Multiple Myeloma, Prognosis

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750