Fan Liping, Hong Jinquan, Huang Haobo, Fu Danhui, Wu Shunquan, Wang Qingqing, Ye Yamei, Liu Yun
Department of Blood Transfusion, Fujian Medical University Union Hospital, Fuzhou, Fujian, China (mainland).
Department of Anesthesia, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China (mainland).
Med Sci Monit. 2017 May 30;23:2636-2643. doi: 10.12659/msm.901850.
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.
背景 先前的研究表明，细胞外信号调节激酶（MEK）/细胞外信号调节激酶（ERK）信号通路在多发性骨髓瘤（MM）患者中通常被激活。然而，MEK/ERK信号通路激活在新诊断MM患者中的预后价值尚未见报道。材料与方法 采用免疫组织化学分析60例新诊断MM患者骨髓活检标本中p-ERK1/2蛋白的表达水平，并分为3组：p-ERK1/2高表达组、p-ERK1/2低表达组和阴性组。采用单因素和多因素分析方法分析包括p-ERK1/2蛋白表达水平、无进展生存期（PFS）和总生存期（OS）在内的临床病理特征之间的相关性。结果 47例骨髓标本中磷酸化-ERK1/2蛋白呈阳性，其中p-ERK1/2高表达标本19例，p-ERK1/2低表达标本28例。单因素Kaplan-Meier分析显示，在新诊断的MM患者中，p-ERK1/2高表达、国际分期系统（ISS）高分期、血清肌酐（Scr）≥177 μmol/l、血清β2微球蛋白（β2-MG）≥5.5 μmol/l和血清钙（Ca）≥2.75 mmol/l与较短的OS和PFS显著相关。此外，东部肿瘤协作组（ECOG）高评分（2-4分）与新诊断MM患者较短的PFS相关。多因素Cox回归分析显示，在新诊断的MM患者中，p-ERK1/2高表达与较短的OS和PFS显著相关。此外，在新诊断的MM患者中，血清Ca≥2.75 mmol/l与较短的PFS显著相关，血清β2-MG≥5.5 μmol/l与较短的OS显著相关。结论 p-ERK1/2高表达是新诊断MM患者预后不良的独立因素。
