非小细胞肺癌患者血清TK1检测及与EGFR靶向治疗疗效观察

Preliminary Observation of Relationship between Serum Thymidine Kinase 1 Level and EGFR Targeted Therapeutic Effect of Patients with Non-small Cell Lung Cancer

目的 探讨非小细胞肺癌(NSCLC)患者血清胸苷激酶1(TK1)水平及靶向治疗前后TK1水平变化与疗效的相关性。方法 选取我院收治的40例晚期NSCLC患者为观察组,40例健康体检者作为对照组,采用免疫印迹增强化学发光法检测两组血清TK1水平。分析NSCLC患者TK1水平与各临床参数的关系,并比较EGFR靶向治疗前及治疗后1、3、6个月的TK1水平,进一步分析TK1与EGFR靶向治疗疗效的相关性。结果 观察组患者血清TK1平均水平为(3.26±0.50)PM·L^-1,显著高于对照组(0.86±0.27)PM·L^-1,差异有统计学意义(P=0.001)。观察组患者血清TK1水平与年龄、性别、病理类型均无明显相关性(P>0.05);与原发肿瘤最大径、淋巴结转移和脏器/骨转移显著相关(P<0.05)。观察组患者血清TK1水平在EGFR靶向治疗后1个月、3个月、6个月的血清TK1水平分别为(2.03±0.14)pM·L^-1、(1.85±0.09)pM·L^-1、(1.61±0.14)pM·L^-1,总体呈下降趋势,组间两两比较,差异均有统计学意义(F=291.646,P=0.000)。在EGFR19del或21L858R突变、靶向治疗有效的NSCLC患者中,血清TK1水平动态变化与EGFR-TKI疗效呈现一致性,EGFR靶向治疗效果好,血清TK1水平显著降低,反之,则TK1水平、居高不下。结论 血清TK1检测在肺癌的早期筛查、临床分期、疗效评估、预后判断、复发监测方面,具有重要应用价值,值得临床推广使用。

Objective To investigate the changes of serum thymidine kinase 1(TK1) level and the relationship between TK1 and targeted therapeutic effect in patients with non-small cell lung cancer (NSCLC). Methods The serum TK1 (S-TK1) levels in 40 healthy controls (control group) and 40 patients with advanced NSCLC (observation group) were detected by immunoblot enhanced chemiluminescence assay (ECLA). The relationship between TK1 level and clinical parameters of NSCLC patients was analyzed, and the differences of TK1 level before EGFRTKI treatment, at 1 month, 3 months and 6 months after EGFR-TKI treatment were compared. Moreover, the correlation between TK1 level and the efficacy of EGFR targeted therapy was further analyzed. Results The mean serum TK1 level of the observation group was (3.26± 0.50) PM·L^-1, significantly higher than that of the control group [(0.86±0.27) PM·L^-1](P=0.001). The serum TK1 level showed no correlation with age (P=0.528), gender (P=0.087) or pathological type (P=0.435) in observation group (P>0.05), but was significantly correlated with the largest diameter of the primary tumor, lymph node metastasis, and visceral organ and/or bone metastasis (P<0.05). Serum TK1 levels in the observation group were respectively (2.03±0.14) PM·L^-1,(1.85±0.09) PM·L^-1 and (1.61±0.14) PM·L^-1 at 1 month, 3 months and 6 months after EGFR-targeted therapy, showing an overall downtrend. After 1 month, 3 and 6 months of EGFR-targeted therapy, the serum TK1 levels in the observation group were compared in pairs, and the differences were statistically significant (F=291.646, P=0.000). In NSCLC population with EGFR 19del or 21L858R mutation and effective targeted therapy, the dynamic change of serum TK1 level was consistent with the effect of EGFR-TKI treatment. That is, reduced serum TK1 level was accompanied with good effect of EGFR-TKI treatment. Conclusion Serum TK1 detection had important clinical application value in early screening, differentiating clinical stage, efficacy evaluation, prognosis judgment and relapse monitoring of lung cancer patients. It could be popularized in clinical practice.