1 上海交通大学附属第六人民医院呼吸危重症科，上海 200233
2 上海市同济医院/同济大学附属同济医院呼吸与危重症医学科，上海 200065
|| 上海市卫生健康委员会科研课题 (202040374)。
目的：探究中期因子(midkine，MK)联合CYFRA21-1评估手术治疗的非小细胞肺癌(non-small cell lung cancer，NSCLC)患者预后的意义。方法：以2016年1月至2017年1月上海交通大学附属第六人民医院手术治疗的134例NSCLC患者为研究对象。检测患者治疗前血清MK和CYFRA21-1水平。以全因死亡作为随访终点，通过受试者工作特征曲线明确MK和CYFRA21-1的最佳切割值，并使用Cox比例风险回归模型分析影响手术治疗的NSCLC患者总生存期的独立危险因素。结果：血清MK和CYFRA21-1鉴别NSCLC患者预后结局的曲线下面积(area under the curve，AUC)分别为0.81和0.72。两者串联使用，鉴别特异性提高至88.0%，并联使用敏感性提高至89.8%。与MK≤833.4 pg/mL组相比，MK>833.4 pg/mL组患者TNM分级更高、细胞分化程度更低。Kaplan-Meier生存曲线提示MK>833.4 pg/mL组患者中位整体生存期明显短于MK≤833.4 pg/mL组(31个月 vs 54个月，P<0.001)；CYFRA21-1>6.89 μg/L组患者中位整体生存期明显短于CYFRA21-1≤6.89 μg/L组(35个月 vs 52个月，P<0.001)。多因素Cox回归分析发现患者TNM分期、肿瘤分化程度、MK>833.4 pg/mL(HR=1.14，P<0.001)以及CYFRA21-1>6.89 μg/L(HR=1.51，P=0.03)是影响患者总生存期的独立危险因素。结论：MK和CYFRA21-1是手术治疗的NSCLC患者总生存期的独立危险因素。两者联合使用有助于提高评估患者预后结局的特异度和敏感度。
Evaluation of preoperative midkine combined with CYFRA21-1 on prognosis of patients with non-small cell lung cancer
CorrespondingAuthor: YANG Zhongmin
This work was supported by the Scienti c Research Project of Shanghai Municipal Health Commission, China (202040374).
Objective: To explore the prognostic significance of midkine (MK) in combination with CYFRA21-1 for the assessment of patients with non-small cell lung cancer (NSCLC) receiving surgical resection. Methods: A total of 134 patients who underwent surgical resection for NSCLC at the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University during January 2016 to January 2017 were selected as the study participants. Serum MK and CYFRA21-1 levels were measured prior to the initiation of any treatments. Patients were followed-up with the primary end point of all-cause mortality. The receiver operating characteristic (ROC) curve was utilized to determine the optima cut-off points for MK and CYFRA21-1, respectively. The Cox proportional hazards model was employed to identify independent risk factors for NSCLC patients receiving surgical resection. Results: The area under the curve for discriminating NSCLC outcome by MK and CYFRA21-1 were 0.81 and 0.72, respectively. Combination in serial would increase specificity to 88.0% and combination in parallel would yield an improved sensitivity of 89.8%. Compared with patients in the MK ≤833.4 pg/mL, patients with MK >833.4 pg/mL showed increased TNM grade and poorer cellular differentiation histopathologically. Survival analysis by the Kaplan-Meier curve indicated that patients with MK >833.4 pg/mL had significantly shorter overall median survival than patients with MK ≤833.4 pg/mL (31 months vs 54 months, P<0.001). In addition, patients with CYFRA21-1 >6.89 μg/L showed significantly shorter overall median survival than those with CYFRA21-1 ≤6.89 μg/L (35 months vs 52 months, P<0.001). Multivariate Cox regression analysis indicated that the TNM classification, tumor differentiation degree, MK >833.4 pg/mL (HR =1.14, P<0.001) and CYFRA21-1 >6.89 μg/L (HR =1.51, P=0.03) were independent risk factors for patient all-cause mortality. Conclusion: The preoperative MK and CYFRA21-1 were independent risk factors for NSCLC patients treated with surgical resection. Combined use of these 2 parameters would increase the specificity and sensitivity to discriminate the outcome of patients with NSCLC.
non-small cell lung cancer; midkine; CYFRA21-1; prognosis