非小细胞肺癌微波消融术后血清Caspase-4变化及意义

doi:10.3877/cma.j.issn.1674-6902.2020.02.019

目的

探讨非小细胞肺癌(NSCLC)患者微波消融术后血清半胱天冬酶(Caspase-4)变化及意义。

方法

选择2013年3月至2016年1月我院及省肿瘤医院收治的159例NSCLC患者作为研究对象，所有患者均接受微波消融治疗。采用活性荧光法测定检测NSCLC患者微波消融治疗前后血清Caspase-4水平。比较不同预后NSCLC患者血清Caspase-4水平。采用受试者工作特征(ROC)曲线分析血清Caspase-4评估NSCLC患者预后的价值。比较不同血清Caspase-4水平NSCLC患者平均生存时间，并采用Cox单因素及多因素分析影响NSCLC患者预后的相关因素。

结果

NSCLC患者微波消融术后血清Caspase-4水平明显低于术前，差异有统计学意义(3.51±0.82)ng/ml vs. (4.33±0.96)ng/ml，P<0.05。死亡组NSCLC患者血清Caspase-4水平高于生存组，差异有统计学意义(5.01±0.63)ng/ml vs. (3.04±0.47)ng/ml，P<0.05。微波消融术后血清Caspase-4评估NSCLC患者预后的AUC、敏感度、特异性分别为0.851、65.79%、90.91%。Caspase-4≥3.17 ng/ml的NSCLC患者平均生存时间明显低于Caspase-4<3.17 ng/ml的NSCLC患者，差异有统计学意义30.19(95%CI：27.84～32.49)个月vs. 33.19(95%CI：31.77～34.60)个月，P<0.05。Cox单因素分析显示年龄、病理类型、分化程度、TNM分期、淋巴结转移、Caspase-4水平与NSCLC预后可能有关(P<0.05)，进一步Cox多因素回归分析显示TNM分期、淋巴结转移、Caspase-4水平与NSCLC患者预后密切相关(P<0.05)。

结论

微波消融术后NSCLC患者血清Caspase-4水平明显降低，血清Caspase-4水平与NSCLC患者预后密切相关，检测术后血清Caspase-4水平对于评估NSCLC患者预后具有重要临床意义。

关键词: 非小细胞肺癌, 微波消融术, 血清半胱天冬酶-4, 预后

Objective

To investigate the changes and significance of serum cysteinyl aspartate specific proteinase-4 (Caspase-4) in patients with non-small cell lung cancer (NSCLC) after microwave ablation.

Methods

One hundred and fifty-nine patients with NSCLC admitted to our hospital and Provincial Cancer Hospital from March 2013 to January 2016 were selected as the subjects of study. All patients received microwave ablation. Serum Caspase-4 levels were measured by active fluorescence method in patients with NSCLC before and after radiofrequency ablation. Serum Caspase-4 levels in NSCLC patients with different prognosis were compared. The prognostic value of serum Caspase-4 in patients with NSCLC was analyzed by ROC curve. The mean survival time of NSCLC patients with different serum Caspase-4 levels was compared. Cox single factor and multi-factor analysis were used to analyze the related factors affecting the prognosis of patients with NSCLC.

Results

The serum Caspase-4 level of NSCLC patients after microwave ablation was significantly lower than that before operation, and the difference was statistically significant [(3.51±0.82) ng/ml vs. (4.33±0.96) ng/ml, P<0.05]. The serum Caspase-4 level of NSCLC patients in death group was significantly higher than that in survival group, and the difference was statistically significant [(5.01±0.63) ng/ml vs. (3.04±0.47) ng/ml, P<0.05]. The AUC, sensitivity and specificity of serum Caspase-4 in evaluating the prognosis of NSCLC patients after microwave ablation were 0.851, 65.79% and 90.91%, respectively. The average survival time of NSCLC patients with Caspase-4≥3.17 ng/ml was significantly lower than that of NSCLC patients with Caspase-4<3.17 ng/ml, and the difference was statistically significant [30.19 (95%CI: 27.84~32.49) months vs. 33.19 (95%CI: 31.77~34.60) months, P<0.05]. Cox univariate analysis showed that age, pathological type, degree of differentiation, TNM stage, lymph node metastasis, Caspase-4 levels might be related to the prognosis of NSCLC (P<0.05). Further Cox multivariate regression analysis showed that the TNM stages, lymph node metastasis and Caspase-4 were closely related to the prognosis of NSCLC patients (P<0.05).

Conclusion

The serum Caspase-4 level was significantly decreased in NSCLC patients after microwave ablation. The serum Caspase-4 level was closely related to the prognosis of NSCLC patients. Detecting the serum Caspase-4 level after microwave ablation has important clinical significance for evaluating the prognosis of NSCLC patients.

Key words: Non-small cell lung cancer, Microwave ablation, Serum cysteinyl aspartate specific proteinase-4, Prognosis

图1 血清Caspase-4评估患者预后的ROC曲线

图2 Caspase-4≥3.17 ng/ml及Caspase-4<3.17 ng/ml NSCLC患者生存曲线

表1 影响NSCLC患者预后的相关因素

临床资料	Cox单因素			Cox多因素
临床资料	HR	95%CI	P值	HR	95%CI	P值
性别(男/女)	1.358	0.873～1.827	0.146	-	-	-
年龄(≥60/<60岁)	2.384	1.046～4.277	0.042	1.738	0.951～2.591	0.077
病理类型(鳞癌/腺癌/腺鳞癌)	2.278	1.016～3.830	0.049	1.560	0.846～2.153	0.085
淋巴结转移(有/无)	2.595	1.104～5.210	0.038	2.285	1.020～3.447	0.048
分化程度(低分化/高分化)	3.204	1.231～5.883	0.031	2.535	1.074～4.827	0.039
TNM分期(Ⅲ～Ⅳ/Ⅰ～Ⅱ)	3.629	1.337～7.021	0.020	2.220	1.219～3.530	0.051
Caspase-4(≥3.17/<3.17 ng/ml)	4.105	1.439～7.492	0.014	3.683	1.332～6.50	0.022

表1 影响NSCLC患者预后的相关因素

临床资料	Cox单因素			Cox多因素
临床资料	HR	95%CI	P值	HR	95%CI	P值
性别(男/女)	1.358	0.873～1.827	0.146	-	-	-
年龄(≥60/<60岁)	2.384	1.046～4.277	0.042	1.738	0.951～2.591	0.077
病理类型(鳞癌/腺癌/腺鳞癌)	2.278	1.016～3.830	0.049	1.560	0.846～2.153	0.085
淋巴结转移(有/无)	2.595	1.104～5.210	0.038	2.285	1.020～3.447	0.048
分化程度(低分化/高分化)	3.204	1.231～5.883	0.031	2.535	1.074～4.827	0.039
TNM分期(Ⅲ～Ⅳ/Ⅰ～Ⅱ)	3.629	1.337～7.021	0.020	2.220	1.219～3.530	0.051
Caspase-4(≥3.17/<3.17 ng/ml)	4.105	1.439～7.492	0.014	3.683	1.332～6.50	0.022

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Changes and significance of serum Caspase-4 in patients with non-small cell lung cancer after microwave ablation

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Changes and significance of serum Caspase-4 in patients with non-small cell lung cancer after microwave ablation