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

doi:10.3877/cma.j.issn.1674-6902.2024.04.003

Abstract

Abstract:

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

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.

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References 29

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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
V_5Gy	21.32(17.36，23.65)	18.35(14.29，23.40)	－1.334	0.182
V_20Gy	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

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
V_5Gy	21.32(17.36，23.65)	18.35(14.29，23.40)	－1.334	0.182
V_20Gy	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

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

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

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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