中国呼吸与危重监护杂志

中国呼吸与危重监护杂志

血清可溶 CD146 在判定肺腺癌 EGFR-TKI 获得性耐药中的作用

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目的探讨血清可溶 CD146(soluble CD146,sCD146)判定肺腺癌表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)耐药的价值。方法选取 2016 年 1 月至 2016 年 12 月在郑州大学人民医院确诊的肺腺癌 EGFR 敏感患者 144 例,根据服用 TKI 药物时间的不同将其分为未服药组(31 例)、服药治疗 1~3 个月组(25 例)、服药治疗 4~6 个月组(19 例)、服药治疗 7~12 个月组(25 例)、服药治疗耐药组(24 例)以及服药治疗超过 1 年未耐药组(20 例)。采用 ELISA 和电化学发光法检测患者血清 sCD146、癌胚抗原(carcinoembryonic antigen,CEA)和神经元特异性烯醇化酶(neuron-specific enolase,NSE)水平,比较血清 sCD146、CEA、NSE 在不同服药时间段的差异,同时分析血清 sCD146 与肿瘤标志物 CEA、NSE 以及肿瘤临床相关指标(年龄、性别、肿瘤分期、有无远处转移、肿瘤直径、病灶数量)的关系。结果未服药组血清 sCD146 水平最低,与其他所有组比较差异有统计学意义(均 P<0.05);服药治疗 1~3 个月组血清 sCD146 水平最高(即服药初期水平最高),随着服药时间的延长且在未耐药前血清 sCD146 水平有下降趋势但差异无统计学意义(P>0.05)。耐药组 sCD146 水平较所有服药未耐药组水平有明显下降趋势(均P<0.05),但仍显著高于未服药组(P<0.05)。服药治疗超过 1 年未耐药组血清 sCD146 水平与服药治疗在 1 年内未耐药组水平相当(P>0.05),且显著高于未服药组和耐药组水平(均P<0.05)。六组间的血清 CEA 水平差异无统计学意义(P>0.05)。血清 NSE 水平 4~6 个月组与 7~12 个月组差异有统计学意义(P<0.05),但均在正常参考值范围内,其余组差异无统计学意义(均P>0.05)。血清 sCD146 与血清 CEA、NSE 无相关性,与性别、年龄、肿瘤分期、肿瘤直径、病灶数量也均无相关性(均P>0.05),与有无远处转移有相关性(P<0.05)。结论sCD146 可能参与了 TKI 杀伤肿瘤细胞的作用机制以及 TKI 的耐药机制,并有望成为监测 TKI 药效和判断 TKI 耐药的血清学指标。

ObjectiveTo investigate the value of serum soluble CD146 (sCD146) in determining acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in lung adenocarcinoma.MethodsA total of 144 lung adenocarcinoma EGFR sensitive patients in People’s Hospital of Zhengzhou University diagnosed from January 2016 to December 2016 were recruited in the study. According to the different time of taking drugs, the patients were divided into a non-medication group (31 cases), a 1 to 3 month treatment group (25 cases), a 4 to 6 month treatment group (19 cases), a 7 to 12 month treatment group (25 cases), a drug-resistant group (24 cases), and a nonresistant group up to 1 year of treatment (20 cases). The serum levels of sCD146, carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) were measured by ELISA and chemiluminescence and compared between different period of medication. The relationship of serum sCD146 with tumor markers (CEA, NSE) and tumor related clinical parameters (age, gender, tumor stage, metastasis, tumor diameter, number of the lesions) were analyzed.ResultsThe serum sCD146 level was minimum in the non-medication group that did not receive pioglitazone treatment, highest in the 1 to 3 month treatment group (early treatment period), and declined with duration of medication until resistance occurred without significant difference (P>0.05). The level of sCD146 of the drug-resistant group was significantly lower than that of all nonresistant groups, with significant difference (allP<0.05), but still higher than that of the non-medication group (P<0.05). The serum sCD146 levels in the nonresistant patients with medication over 1 year and within 1 year were similar (P>0.05), and significantly higher than the non-medication group and drug-resistance group (allP<0.05). The serum CEA levels did not differ significantly between 6 groups (P>0.05). The serum NSE level of the 4 to 6 month treatment group was lower than that of the 7 to 12 month treatment group (P<0.05), but both in the normal reference range. The NSE levels did not differ in any other groups (P>0.05). Serum sCD146 was associated with metastasis (P<0.05), but not associated with serum CEA or NSE, nor with sex, age, tumor staging, tumor diameter or lesion number (allP>0.05).ConclusionsCD146 may be involved in the mechanism of TKI killing tumor cells and the mechanism of TKI resistance, and may be a serological marker for monitoring the efficacy of TKI and judging the resistance of TKI.

关键词: 可溶 CD146; 肺腺癌; 表皮生长因子受体-酪氨酸激酶抑制剂; 获得性耐药

Key words: Soluble CD146; Lung adenocarcinoma; Epidermal growth factor receptor-tyrosine kinase inhibitor; Acquired drug resistance

引用本文: 刘畅, 马利军. 血清可溶 CD146 在判定肺腺癌 EGFR-TKI 获得性耐药中的作用. 中国呼吸与危重监护杂志, 2018, 17(2): 155-160. doi: 10.7507/1671-6205.201709021 复制

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