| 唐川,邱玲.血清葡萄糖调节蛋白 78在多发性骨髓瘤病人中的表达及其预后意义[J].安徽医药,2024,28(9):1773-1777. |
| 血清葡萄糖调节蛋白 78在多发性骨髓瘤病人中的表达及其预后意义 |
| The expression level of serum GRP78 and its prognostic significance in multiple myeloma patients |
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| DOI：10.3969/j.issn.1009-6469.2024.09.017 |
| 中文关键词: 多发性骨髓瘤 葡萄糖调节蛋白 78 硼替佐米 β2-微球蛋白 治疗反应 预后 |
| 英文关键词: Multiple myeloma Glucose regulated protein 78 Bortezomib Beta2-microglobulin Treatment response Prognostic |
| 基金项目:四川省科技计划项目( 2021YJ0145) |
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| 中文摘要: |
| 目的探讨葡萄糖调节蛋白 78(GRP78)在初诊多发性骨髓瘤(MM)病人血清中的表达，及其对病人治疗反应及预后的预测价值。方法选择 2017年 1月至 2020年 12月大竹县人民医院收治的 78例 MM病人为 MM组，同期该院门诊就诊的 62例健康成人作为对照组。收集所有参与者的外周静脉血样本，使用酶联免疫吸附测定( ELISA)法检测血清中 GRP78的表达，分析 GRP78表达与临床特征及治疗反应的关系。通过受试者操作特征曲线(ROC曲线)确定血清 GRP78预测 MM病人预后的最佳临界值，采用 Kaplan-Meier曲线与 Cox比例风险模型评估血清 GRP78表达与 MM病人预后的关系。结果 MM病人的血清 GRP78表达水平显著高于对照组(Z=4.12，P<0.001)中位表达量分别为 2.49(1.23，5.13)mg/L和 1.29(0.75，2.14)mg/L。与多发性骨髓瘤国际预后分期( ISS)Ⅰ、Ⅱ期病人2.，05(1.09，4，.40)mg/L相比，血清 GRP78表达在 ISS Ⅲ期病人 2.99(1.66，5.63)mg/L显著升高(Z=2.18，P=0.030)。然而，血清 GRP78表达与接受硼替佐米诱导方案的 MM病人的治疗反应无关。 ROC曲线显示血清 GRP78预测总体生存( OS)的最佳临界值为 1.68 mg/L，曲线下面积( AUC)为 0.70，95%CI:(0.58，0.81)，灵敏度与特异度分别为 78.7%和58.4%。Kaplan-Meier曲线表明 GRP78高表达(≤1.68 mg/L，n=50)组生存期明显短于低表达组(>1.68 mg/L，n=28)，差异有统计学意义( χ2=10.99，P=0.001)。单、多因素 Cox分析揭示 ISS分期［HR=2.04，95%CI:(1.11，3.76)，P=0.022］、治疗反应［HR=2.42， 95%CI:(1.28，4.58)P=0.007］和血清 GRP78表达［HR=2.96，95%CI:(1.43，6.12)，P=0.003］是 MM病人血清的独立预后因素。结论 GRP78在 MM病人中呈现异常高表达，且与 ISS分期及不良预后有关，或许是 MM诊断与预后风险分层的重要标志物。 |
| 英文摘要: |
| Objective To investigate the expression level of serum glucose regulated protein 78 (GRP78) and its predictive value oftreatment response and prognosis for newly diagnosed multiple myeloma (MM) patients.Methods This study included 78 MM patientsadmitted to Dazhu County People's Hospital from January 2017 to December 2020, and 62 healthy adults who visited outpatient depart-ment during the same period were recruited as the control group. The peripheral blood samples of all participants were collected, andthe expression level of serum GRP78 was detected by enzyme-linked immunosorbent assay (ELISA). The relationships between serumGRP78 expression and clinical parameters as well as treatment response were analyzed. The optimal threshold of serum GRP78 expres-sion for predicting the prognosis of MM patients was determined by receiver operating characteristics (ROC) curve. The Kaplan-Meier curves and the Cox proportional risk regression model were used to evaluate the relationship between the expression of serum GRP78and the prognosis of MM patients.Results The expression level of serum GRP78 in MM patientswas significantly higher than that in the control group [2.49 (1.23,5.13) mg/L vs. 1.29 (0.75,2.14) mg/L] (Z=4.12, P<0.001). The MM patients with International Staging Sys- tem (ISS) stage Ⅲ had a higher expression level than those with stage Ⅰ-Ⅱ [2.99 (1.66,5.63) mg/L vs. 2.05 (1.09,4.40) mg/L] (Z=2.18, P=0.030). However, the expression of serum GRP78 was not associated with treatment response of MM patients who received a bortezo-mib-based induction regimen. The ROC curve showed that optimal threshold of serum GRP78 expression for survival prediction was 1.68 mg/L, and the area under the curve (AUC) value was 0.70 95%CI: (0.58,0.81), with the sensitivity of 78.7% and the specificity of 58.4%, respectively. The Kaplan-Meier curves indicated that patients with high expression of serum GRP78 (≤1.68 mg/L, n=50) hadshorter OS than those in low expression group (>1.68 mg/L, n=28), with a significant statistical difference (χ2=10.99, P=0.001). The uni- variate and multivariate Cox analysis results revealed that ISS staging [HR=2.04, 95%CI:(1.11,3.76), P=0.022], treatment response [HR =2.42, 95%CI:(1.28,4.58), P=0.007], and the expression level of serum GRP78 [HR=2.96, 95%CI:(1.43,6.12), P=0.003] were indepen- dent prognostic factors for MM patients.Conclusions Serum GRP78 was significantly overexpressed in MM patients as compared tohealthy controls, and its high expression was associated with ISS staging and poor survival. Serum GRP78 expression might be an im-portant biomarker for clinical diagnosis and prognostic stratification of MM patients. |
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