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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2024, Vol. 17 ›› Issue (04) : 519 -523. doi: 10.3877/cma.j.issn.1674-6902.2024.04.003

论著

晚期非小细胞肺癌血清Ape1/Ref-1对放射性肺损伤发生的预测意义
张桂萍1, 丘勇林1, 湛绮婷1, 孙乐栋1,†()   
  1. 1. 510900　广州，南方医科大学第五附属医院全科医学科
  • 收稿日期:2024-01-13 出版日期:2024-08-25
  • 通信作者: 孙乐栋
  • 基金资助:
    广东省医学科学技术研究基金项目(B2023096)

Prognostic significance of serum Ape1/Ref-1 for the radioactive lung injury in patients with advanced non-small cell lung cancer

Guiping Zhang1, Yonglin Qiu1, Qiting Zhan1, Ledong Sun1,†()   

  1. 1. Department of General Practice, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510900, China
  • Received:2024-01-13 Published:2024-08-25
  • Corresponding author: Ledong Sun
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引用本文：

张桂萍, 丘勇林, 湛绮婷, 孙乐栋. 晚期非小细胞肺癌血清Ape1/Ref-1对放射性肺损伤发生的预测意义[J]. 中华肺部疾病杂志(电子版), 2024, 17(04): 519-523.

Guiping Zhang, Yonglin Qiu, Qiting Zhan, Ledong Sun. Prognostic significance of serum Ape1/Ref-1 for the radioactive lung injury in patients with advanced non-small cell lung cancer[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(04): 519-523.

目的

分析局部晚期非小细胞肺癌(locally advanced non-small cell lung cancer, LA-NSCLC)放疗患者血清脱嘌呤/脱嘧啶核酸内切酶1(Apurinic/apyrimidinic endonuclease 1, Ape1)/氧化还原效应因子1(redox factor-1, Ref-1)对放射性肺损伤(radiation-induced lung injury ，RILI)发生的预测。

方法

选择2019年1月至2022年1月我院收治的经同步放化疗(concurrent chemoradiotherapy, CCRT)76例LA-NSCLC患者。胸部CT扫描表现RILI 17例为观察组，无RILI 59例为对照组。放疗前后搜集血清样本，采用双抗体夹心酶联免疫吸附试验测定血清中Ape1/Ref-1，分析在RILI中的预测。

结果

观察组肿瘤直径21.0(20.0，27.0)mm、肿瘤位于上叶14例(82.35%)、放疗总剂量64.0(60.0，65.0)Gy高于对照组肿瘤直径19.0(16.0，23.0)mm、肿瘤位于上叶26例(44.07%)、放疗总剂量60.0(59.0，61.0)Gy(P<0.05)。观察组和对照组放疗后血清Ape1/Ref-1增加，观察组血清Ape1/Ref-1 5.90(3.17，9.60)ng/ml高于对照组2.18(1.17，3.95)ng/ml(P<0.05)。多因素Logistic显示血清Ape1/Ref-1≥2.42 ng/ml是治疗后RILI发生的危险因素(P<0.05)。治疗后血清Ape1/Ref-1预测RILI能力强(AUC：0.823，95%CI：0.723～0.922)(P<0.001)。肿瘤直径≥20 mm基线血清Ape1/Ref-1高，放疗总剂量与血清Ape1/Ref-1水平正相关(P<0.05)。CCRT治疗后疾病复发20例，疾病控制56例。放疗后疾病复发和疾病控制者血清Ape1/Ref-1增加，疾病复发者血清Ape1/Ref-1 4.76(2.45，7.11)ng/ml高于疾病控制者2.22(1.18，3.79)ng/ml(P<0.05)。

结论

LA-NSCLC放疗后血清Ape1/Ref-1可预测RILI，放疗后高水平血清Ape1/Ref-1与RILI发生风险增加和不良预后相关。

关键词: 非小细胞肺癌, 脱嘌呤/脱嘧啶核酸内切酶1, 放射性肺损伤, 同步放化疗
Objective

To analyze the predictive effect of serum apurinic/apyrimidinic endonuclease 1 (Ape1)/ redox factor-1 (Ref-1) on the occurrence of radiation-induced lung injury (RILI) in patients with locally advanced non-small cell lung cancer(LA-NSCLC) treated with radiotherapy.

Methods

A total of 76 patients with LA-NSCLC were selected who underwent concurrent chemoradiotherapy (CCRT) in otherapy in our hospital from January 2019 to January 2022. Chest CT scan showed RILI in 17 cases as observation group, no RILI in 59 cases as control group. Serum samples were collected before and after radiotherapy, serum Ape1/Ref-1 was determined by double-antibody sandwich ELISA, and its predictive value in RILI were analyzed.

Results

The tumor diameter in the observation group was 21.0 (20.0, 27.0) mm, the tumor was located in the upper lobe in 14 cases (82.35%), and the total dose of radiotherapy 64.0 (60.0, 65.0) Gy was higher than that in the control group 19.0 (16.0, 23.0)mm 26 cases (44.07%) with tumor located in upper lobe, total dose of radiotherapy was 60.0 (59.0, 61.0) Gy (P<0.05). After radiotherapy, serum Ape1/Ref-1 was increased in observation group and control group, serum Ape1/Ref-15.90 (3.17, 9.60)ng/ml in observation group was higher than that in control group 2.18 (1.17, 3.95) ng/ml(P<0.05). Multivariate Logistic analysis showed that serum Ape1/Ref-1≥2.42 ng/ml was the risk factor for RILI after treatment (P<0.05). After treatment, serum Ape1/Ref-1 had a strong ability to predict RILI (AUC: 0.823, 95%CI: 0.723-0.922)(P<0.001). Tumor diameter ≥20 mm serum Ape1/Ref-1 level was higher at baseline, total radiotherapy dose was positively correlated with serum Ape1/Ref-1 level (P<0.05). After CCRT treatment, the disease recurred in 20 cases, the disease was controlled in 56 cases. After radiotherapy, the serum Ape1/Ref-1 in patients with disease recurrence and disease control increased, the serum Ape1/Ref-14.76 (2.45, 7.11) ng/ml in patients with disease recurrence was higher than that in patients with disease control 2.22 (1.18, 3.79) ng/ml (P<0.05).

Conclusion

Serum Ape1/Ref-1 after radiotherapy in LA-NSCLC can predict RILI, and high levels of serum Ape1/Ref-1 after radiotherapy are associated with increased risk of RILI and poor prognosis.

Key words: Non-small cell lung cancer, Apurinic/apyrimidinic endonuclease 1/redox factor-1, Radiation lung injury, Concurrent chemoradiotherapy
表1 两组NSCLC患者临床资料比较[M50(P25，P75)，(±s)，n(%)]
临床资料 观察组(n＝17例) 对照组(n＝59例) Z/t/χ2 P值
肿瘤直径(mm) 21.0(20.0，27.0) 19.0(16.0，23.0) －2.309 0.021
病理     0.710 0.400
腺癌 12(70.59) 35(59.32)    
鳞癌 5(29.41) 24(40.68)    
肿瘤位置     6.299 0.012
上叶 14(82.35) 26(44.07)    
中/下叶 3(17.65) 33(55.93)    
吸烟指数(包年) 38.0(0.0，60.0) 20.0(0.0，45.0) －1.099 0.272
TNM分期     0.001 0.982
ⅢA 6(35.29) 21(35.59)    
ⅢB 11(64.71) 38(64.41)    
放疗总剂量(Gy) 64.0(60.0，65.0) 60.0(59.0，61.0) －3.405 0.001
单次放疗剂量(Gy) 2.10(2.0，2.40) 2.0(2.0，2.0) －1.471 0.141
PTV(cc) 43.36(32.62，58.83) 43.36(28.92，57.56) －0.212 0.832
V5Gy 21.32(17.36，23.65) 18.35(14.29，23.40) －1.334 0.182
V20Gy 6.36(4.67，7.77) 4.76(3.71，8.07) －1.259 0.208
FVC(L) 2.56±0.41 2.63±0.43 －0.551 0.583
FEV1(L/s) 2.09±0.82 2.02±0.80 －0.305 0.761
FEV1/FVC 0.84±0.34 0.79±0.34 0.480 0.632
表2 Logistic多因素回归分析RILI发生的危险因素
影响因素 β S.E. 瓦尔德 HR(95%CI) P值
肿瘤直径≥20 mm(是vs.否) 1.447 0.802 3.254 4.251(0.882～20.479) 0.071
肿瘤位于上叶(是vs.否) 1.435 0.771 3.465 4.199(0.927～19.026) 0.063
放疗总剂量>60Gy(是vs.否) 1.266 0.730 3.010 3.546(0.849～14.817) 0.083
放疗后Ape1/Ref-1≥2.42 ng/ml(是vs.否) 1.718 0.874 3.868 5.576(1.006～39.906) 0.049
表3 基线血清Ape1/Ref-1与肿瘤特征的关系[ng/ml，M50(P25，P75)]
变　量 基线血清Ape1/Ref-1 Z值 P值
肿瘤直径≥20 mm   －2.031 0.038
是 1.52(0.51，3.73)    
否 0.38(0.22，2.18)    
肿瘤位于上叶   －1.879 0.060
是 1.63(0.38，3.71)    
否 0.76(0.21，3.0)    
肿瘤TNM分期   －0.645 0.519
ⅢA 1.21(0.38，4.22)    
ⅢB 0.95(0.33，2.97)    
放疗总剂量>60Gy   －0.738 0.460
是 1.84(0.30，4.01)    
否 0.85(0.36，2.35)    
单次放疗剂量>2Gy   －0.940 0.347
是 1.34(0.66，2.67)    
否 0.86(0.24，3.35)    
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