摘要： 目的 评估游离的糖蛋白非转移性黑色素瘤蛋白B （GPNMB）对表皮生长因子受体（EGFR）扩增伴随突变的非小细胞肺癌（NSCLC）患者的耐药和预后的预测价值。方法 选取2018年3月至2019年9月在唐山市人民医院接受治疗的55例EGFR扩增伴随突变的NSCLC患者作为观察组，患者均应用EGFR酪氨酸激酶抑制剂（EGFR-TKI）作为一线治疗方案；随机选取同期体检中心67例健康人群血液样本作为对照组。比较2组游离GPNMB表达水平；采用t检验或χ²检验分析GPNMB表达和患者临床病理特征的相关性；结合临床疗效，评估其作为耐药标志物的价值。随访患者的无进展生存时间（PFS），并采用多因素Cox回归分析影响EGFR扩增伴随突变NSCLC患者生存的独立危险因素。结果 与对照组相比，观察组游离GPNMB表达水平显著升高。观察组游离GPNMB水平和EGFR-TKI的临床疗效显著相关（P = 0.016），GPNMB高表达患者的耐药程度更强，PFS也更短（P = 0.032）。游离GPNMB高水平（HR=4.029，95% CI：1.942~8.358，P < 0.001）是影响患者生存的独立危险因素。结论 EGFR扩增伴随突变的NSCLC患者游离GPNMB表达水平显著上调；且其高表达与患者耐药程度的增强及不良预后显著相关，是影响患者生存的独立危险因素。

血清糖蛋白非转移性黑色素瘤蛋白B对表皮生长因子受体扩增伴随突变的非小细胞肺癌预后的预测作用

刘邦卿¹, 李剑锋¹, 刘晓辉¹, 张劲男², 胡亚丽¹

1. 唐山市人民医院胸外二科, 河北 唐山 063001;
2. 唐山市人民医院头颈外科, 河北 唐山 063001

收稿日期:2023-04-21出版日期:2024-02-28发布日期:2024-01-12
通讯作者:刘邦卿E-mail:lkjzf_2188@163.com
作者简介:刘邦卿(1988-),男,主治医师,硕士.
基金资助:河北省2024年度医学科学研究课题（20241213）


关键词: 非小细胞肺癌, 糖蛋白非转移性黑色素瘤蛋白B, 表皮生长因子受体扩增伴随突变, 耐药, 预后
Abstract: Objective To evaluate the clinical value of free glycoprotein non-metastatic melanoma protein B (GPNMB) as a drug resis-tance and prognostic marker for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) amplification accompanied by mutations. Methods Fifty-five cases of NSCLC patients with EGFR amplification associated with mutations who received treatment from March 2018 to September 2019 were included as the observation group. All patients received an EGFR-tyrosine kinase inhibitor (EGFR-TKI) as the first-line treatment; 67 blood samples from the physical examination center during the same period were randomly included as healthy control. We compared the expression levels of free GPNMB between the two groups, explored the correlation between GPNMB expression and the clinicopathological information in the observation group; and combined the clinical efficacy to evaluate its value as a drug resistance marker. Through follow-up, the progress free survival (PFS) of patients was statistically analyzed, and through multivariate Cox regression analysis, independent risk factors affecting the survival in the observation group were explored. Results Compared with that in the control group, the expression level of free GPNMB in the observation group was significantly up-regulated. The expression level of free GPNMB in the observation group is significantly related to the clinical efficacy of EGFR-TKI (P=0.016). Patients with high GPNMB expression have significantly stronger drug resistance, and patients with high GPNMB expression have significantly shorter PFS duration (P=0.032). A high free GPNMB expression (HR=4.029, 95%CI:1.942-8.358, P < 0.001) is also an independent risk factor affecting patient survival. Conclusion The expression level of free GPNMB in patients with EGFR amplification accompanied by mutant NSCLC is significantly up-regulated, and its high expression is significantly related to the enhancement of the patient's drug resistance. High GPNMB expression is significantly related to the poor prognosis of patients and is an independent risk factor affecting patient survival.
Key words: non-small cell lung cancer, glycoprotein non-metastatic melanoma protein B, epidermal growth factor receptor amplification accompanied by mutations, drug resistance, prognosis
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