血清sCD163、IFN-γ联合TGF-β1对NSCLC患者放疗后发生放射性肺炎的早期预测价值

摘要/Abstract

摘要：

目的分析血清可溶性CD163分子（sCD163）、γ-干扰素（IFN-γ）联合转化生长因子-β1（TGF-β1）对非小细胞肺癌（NSCLC）患者放疗后发生放射性肺炎（RP）的早期预测价值。方法选择2020年12月至2023年11月武汉市中医医院收治的临床分期为Ⅲ~Ⅳ期接受放疗的NSCLC患者132例。采用酶联免疫吸附试验检测血清sCD163、IFN-γ、TGF-β1水平。分析患者放疗后RP发生情况，对接受放疗NSCLC患者发生RP与未发生RP患者以及不同级别RP患者血清sCD163、IFN-γ、TGF-β1水平进行比较。采用多因素logistic回归分析NSCLC患者发生RP的影响因素；采用受试者操作特征（ROC）曲线分析血清sCD163、IFN-γ联合TGF-β1对NSCLC放疗患者发生RP的预测价值。结果接受放疗NSCLC患者RP发生率为24.24%（32/132），其中Ⅱ级18例、Ⅲ级12例、Ⅳ级2例。RP患者血清sCD163[（94.30±15.78）pg/ml比（75.43±13.16）pg/ml，t=6.72，P<0.001]、IFN-γ[（6.52±1.54）pg/ml比（4.79±0.94）pg/ml，t=7.65，P<0.001]、TGF-β1[（9.40±2.63）μg/L比（6.30±1.55）μg/L，t=8.18，P<0.001]水平均显著高于无RP患者，差异均有统计学意义。且Ⅲ~Ⅳ级RP患者血清sCD163[（104.44±15.97）pg/ml比（86.41±15.63）pg/ml，t=3.21，P=0.003]、IFN-γ[（7.47±1.56）pg/ml比（5.78±1.52）pg/ml，t=3.09，P=0.004]、TGF-β1[（11.27±2.68）μg/L比（7.94±2.59）μg/L，t=3.55，P=0.001]水平均高于Ⅱ级RP患者，差异均有统计学意义。RP患者与无RP患者放射剂量（χ²=9.25，P=0.002）、V₂₀（t=6.39，P<0.001）、平均肺剂量（MLD）（t=3.57，P<0.001）差异均有统计学意义。多因素分析显示，放射剂量（OR=3.98，95%CI为2.22~7.15，P<0.001）、V₂₀（OR=4.75，95%CI为2.03~11.15，P<0.001）、MLD（OR=3.15，95%CI为1.63~6.09，P=0.001）、sCD163（OR=4.53，95%CI为1.63~12.58，P=0.004）、IFN-γ（OR=5.11，95%CI为2.07~12.65，P<0.001）、TGF-β1（OR=5.55，95%CI为2.99~10.31，P<0.001）均是接受放疗NSCLC患者发生RP的独立影响因素。sCD163、IFN-γ、TGF-β1单独预测接受放疗NSCLC患者发生RP的ROC曲线下面积（AUC）分别为0.81（95%CI为0.72~0.89）、0.83（95%CI为0.75~0.92）、0.84（95%CI为0.76~0.92），三者联合预测接受放疗NSCLC患者发生RP的AUC为0.93（95%CI为0.88~0.99），三者联合预测价值较sCD163（Z=2.57，P=0.005）、IFN-γ（Z=2.02，P=0.021）、TGF-β1（Z=1.94，P=0.026）单独预测更高。结论接受放疗NSCLC患者发生RP后血清sCD163、IFN-γ、TGF-β1水平显著升高，三者联合预测NSCLC患者放疗后发生RP的价值较高。

关键词:癌，非小细胞肺,辐射性肺炎,可溶性CD163分子,γ-干扰素,转化生长因子-β1

Abstract:

ObjectiveTo analyze the early predictive value of serum soluble CD163 （sCD163）， interferon-γ （IFN-γ）， and transforming growth factor-β1 （TGF-β1） for radiation pneumonitis （RP） in non-small cell lung cancer （NSCLC） patients after radiation therapy.MethodsOne hundred and thirty-two NSCLC patients with clinical stage Ⅲ-Ⅳ receiving radiotherapy at Wuhan Hospital of Traditional Chinese Medicine from December 2020 to November 2023 were selected. Serum sCD163， IFN-γ and TGF-β1 levels were detected by enzyme-linked immunosorbent assay. The occurrence of RP after radiotherapy was analyzed； serum sCD163， IFN-γ， and TGF-β1 levels were compared between NSCLC patients receiving radiotherapy who had RP and those who did not， as well as patients with different levels of RP. Multivariate logistic regression was used to analyze the factors affecting the occurrence of RP in NSCLC patients； the predictive value of serum sCD163， IFN-γ combined with TGF-β1 for the occurrence of RP in patients undergoing radiotherapy for NSCLC was analyzed using reciver operator characteristic （ROC） curves.ResultsThe incidence of RP in NSCLC patients receiving radiotherapy was 24.24% （32/132）. There were 18 cases of grade Ⅱ， 12 cases of grade Ⅲ， 2 cases of grade Ⅳ. Serum sCD163 levels in patients with RP [（94.30±15.78） pg/mlvs.（75.43±13.16） pg/ml，t=6.72，P<0.001]， IFN-γ [（6.52±1.54） pg/mlvs.（4.79±0.94） pg/ml，t=7.65，P<0.001]， TGF-β1 [（9.40±2.63） μg/Lvs.（6.30±1.55） μg/L，t=8.18，P<0.001] were significantly higher than those of patients without RP， and there were statistically significant differences. And levels of serum sCD163 [（104.44±15.97） pg/mlvs.（86.41±15.63） pg/ml，t=3.21，P=0.003]， IFN-γ [（7.47±1.56） pg/mlvs.（5.78±1.52） pg/ml，t=3.09，P=0.004] and TGF-β1 [（11.27±2.68） μg/Lvs. （7.94±2.59） μg/L，t=3.55，P=0.001] in RP patients with grade Ⅲ-Ⅳ were higher than those in RP patients with grade Ⅱ， and there were statistically significant differences. There were statistically significant differences in radiation dose （χ²=9.25，P=0.002）， V₂₀（t=6.39，P<0.001） and mean lung dose （MLD）（t=3.57，P<0.001） between patients with and without RP. Multivariate analysis showed that radiation dose （OR=3.98， 95%CI： 2.22-7.15，P<0.001）， V₂₀（OR=4.75， 95%CI： 2.03-11.15，P<0.001）， MLD （OR=3.15， 95%CI： 1.63-6.09，P=0.001）， sCD163 （OR=4.53， 95%CI： 1.63-12.58，P=0.004）， IFN-γ （OR=5.11， 95%CI： 2.07-12.65，P<0.001）， and TGF-β1 （OR=5.55， 95%CI： 2.99-10.31，P<0.001） were the independent influencing factors for developing RP in patients receiving radiotherapy for NSCLC. The area under the curve （AUC） of sCD163， IFN-γ， and TGF-β1 alone for predicting the occurrence of RP in patients receiving radiotherapy for NSCLC was 0.81 （95%CI： 0.72-0.89）， 0.83 （95%CI： 0.75-0.92） and 0.84 （95%CI： 0.76-0.92）， and the AUC of the above three combined for predicting the occurrence of RP in NSCLC patients receiving radiotherapy was 0.93 （95%CI： 0.88-0.99）， and the combined predictive value of the three was higher than that of sCD163 （Z=2.57，P=0.005）， IFN-γ （Z=2.02，P=0.021）， and TGF-β1 （Z=1.94，P=0.026） alone.ConclusionSerum sCD163， IFN-γ， and TGF-β1 levels are significantly elevated in NSCLC patients undergoing radiotherapy who develop RP， and the combination of the three is of high value in predicting the development of RP in NSCLC patients after radiation therapy.

Key words:Carcinoma， non-small-cell lung,Radiation pneumonitis,Soluble CD163,Interferon-γ,Transforming growth factor-β1

黄波, 汪鹏. 血清sCD163、IFN-γ联合TGF-β1对NSCLC患者放疗后发生放射性肺炎的早期预测价值[J]. 国际肿瘤学杂志, 2024, 51(9): 563-568.

Huang Bo, Wang Peng. Early predictive value of serum sCD163， IFN-γ combined with TGF-β1 in the development of radiation-induced pneumonia in NSCLC patients[J]. Journal of International Oncology, 2024, 51(9): 563-568.

图/表6

组别	sCD163（pg/ml）	INF-γ（pg/ml）	TGF-β1（μg/L）
无RP患者（n=100）	75.43±13.16	4.79±0.94	6.30±1.55
RP患者（n=32）	94.30±15.78	6.52±1.54	9.40±2.63
t值	6.72	7.65	8.18
P值	<0.001	<0.001	<0.001

表1

级别	sCD163（pg/ml）	INF-γ（pg/ml）	TGF-β1（μg/L）
Ⅱ级（n=18）	86.41±15.63	5.78±1.52	7.94±2.59
Ⅲ~Ⅳ级（n=14）	104.44±15.97^a	7.47±1.56^a	11.27±2.68^a
t值	3.21	3.09	3.55
P值	0.003	0.004	0.001

表2

表3

影响132例接受放疗NSCLC患者发生RP的单因素分析（例/ $\bar{x}\pm s$）"

因素	RP患者（n=32）	无RP患者（n=100）	χ²/t值	P值	因素	RP患者（n=32）	无RP患者（n=100）	χ²/t值	P值
年龄（岁）					肿瘤最大径（cm）
<60	15	52	0.26	0.614	<3	4	25
≥60	17	48	0.26	0.614	3~5	7	30	4.36	0.113
性别					>5	21	45
女	14	41	0.08	0.784	KPS评分（分）
男	18	59	0.08	0.784	<80	19	43	2.61	0.106
吸烟史					≥80	13	57	2.61	0.106
无	13	50	0.85	0.355	放射剂量（Gy）
有	19	50	0.85	0.355	<60	9	59	9.25	0.002
病理类型					≥60	23	41	9.25	0.002
腺癌	14	44			同期化疗
鳞状细胞癌	13	40	0.01	0.998	无	6	16	0.13	0.716
其他	5	16			有	26	84	0.13	0.716
肿瘤部位					V₅（%）	49.28±10.35	51.34±11.13	1.60	0.121
中央型	13	44			V₂₀（%）	25.64±7.11	20.31±6.42	6.39	<0.001
周围型	9	25	0.16	0.925	V₃₀（%）	16.81±4.92	15.92±4.87	1.48	0.141
弥漫型	10	31			MLD（Gy）	1 365.15±336.48	1 221.94±315.96	3.57	<0.001
TNM分期
Ⅲ期	18	73	3.18	0.075
Ⅳ期	14	27	3.18	0.075

表3

因素	β值	SE值	Waldχ²值	OR值	95%CI	P值
放射剂量	1.38	0.30	21.52	3.98	2.22~7.15	<0.001
V₂₀	1.56	0.44	12.84	4.75	2.03~11.15	<0.001
MLD	1.15	0.34	11.67	3.15	1.63~6.09	0.001
sCD163	1.51	0.52	8.41	4.53	1.63~12.58	0.004
IFN-γ	1.63	0.46	12.48	5.11	2.07~12.65	<0.001
TGF-β1	1.71	0.32	29.43	5.55	2.99~10.31	<0.001

表4

指标	AUC	95%CI	截断值	敏感性（%）	特异性（%）
sCD163	0.81	0.72~0.89	82.97 pg/ml	71.90	74.00
IFN-γ	0.83	0.75~0.92	5.44 pg/ml	81.30	76.00
TGF-β1	0.84	0.76~0.92	8.15 μg/L	71.90	86.00
三者联合	0.93	0.88~0.99	-	90.60	73.00

表5

图1

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