摘要
目的分析肺癌立体定向放疗(stereotactic body radiation therapy,SBRT)前后血清淀粉样蛋白P(serum amyloid P,SAP)和基质金属蛋白酶(matrix metalloproteinases,MMPs)表达变化,与放射性肺损伤(radiation-induced lung injury,RILI)及预后相关性。方法选择2020年1月至2023年8月我院收治的经SBRT肺癌患者75例为对象发生RILI 21例为观察组,未发生RILI 54例为对照组。使用酶联免疫吸附试验法检测血清SAP及MMPs(MMP1、MMP2、MMP9)水平。SBRT后随访记录无进展生存期(progression-free survival,PFS)、总生存期(overall survival,OS)、局部无进展生存期(local progression-free survival,LPFS)和无远处转移生存期(distant metastasis-free survival,DMFS)。根据不良事件通用术语标准(CTCAE 5.0)判断放疗后6个月内RILI(CTCAE≥2级)发生率。结果观察组放疗前血清SAP水平14.67(11.21,19.21)μg/ml低于对照组27.62(24.33,32.60)μg/ml,MMP-1观察组21.70(12.20,30.45)ng/ml、MMP-2701.00(620.50,846.00)ng/ml、MMP-96.80(2.00,10.30)ng/ml高于对照组MMP-110.60(7.65,16.25)ng/ml、MMP-2912.00(779.00,1100.00)ng/ml、MMP-921.60(10.70,66.50)ng/ml(P<0.05)。放疗前血清SAP、MMP-1、MMP-2、MMP-9水平预测SBRT后RILI的ROC曲线下面积分别为0.881、0.784、0.760、0.885。血清SAP水平SBRT前23.42(17.27,28.57)μg/ml较SBRT后血清SAP水平30.09(23.51,39.86)μg/ml升高,MMP-1SBRT前13.10(8.30,21.70)ng/ml、MMP-2757.00(660.00,880.00)ng/ml、MMP-96.60(2.40,17.20)ng/ml较SBRT后10.50(7.00,16.80)ng/ml、MMP-2690.00(604.00,810.00)ng/ml、MMP-92.00(2.80,3.40)ng/ml降低(P<0.05)。75例中死亡63例(84.00%),生存12例(16.00%)。单因素和多因素COX回归分析显示,放疗前血清SAP和MMP-1、MMP-2、MMP-9是PFS、OS和DMFS的影响因素(P<0.05),放疗前血清SAP和MMP-9是LPFS的影响因素(P<0.05)。Kaplan-Meier分析显示,与放疗前高SAP和低MMPs相比,低SAP和高MMPs患者的PFS率和OS率低,中位PFS和OS时间短(P<0.05)。放疗前血清SAP和MMPs联合风险模型中,与低风险患者相比,高风险患者PFS和OS率低,中位PFS和OS时间短(P<0.05)。结论放疗前低SAP和高MMPs水平与SBRT后RILI和不良预后高风险有关。放疗前血清SAP和MMPs可作为肺癌患者SBRT后RILI和预后不良的生物标志物。
Objective To investigate the changes of serum amyloid P(SAP)and matrix metalloproteinases(MMPs)expression before and after stereotactic body radiation therapy(SBRT)in lung cancer patients and their correlation with radiation-induced lung injury(RILI)and prognosis.Methods A total of 75 patients with lung cancer who received SBRT in our hospital between January 2020 and August 2023 were selected as the study subjects.Serum SAP and MMPs(MMP1,MMP2,MMP9)levels were detected by ELISA.Progression-free survival(PFS),overall survival(OS),local progression-free survival(LPFS),and distant metastasis-free survival(DMFS)were recorded after SBRT.In addition,the incidence of RILI(CTCAE≥grade 2)within 6 months after radiotherapy was assessed according to the Common Terminology Criteria for Adverse Events(CTCAE 5.0).Results The incidence of RILI after SBRT was 28.0%(21/75).The serum SAP level in the observation group before radiotherapy was significantly lower than that in the control group[14.67(11.21,19.21)μg/ml vs.27.62(24.33,32.60)μg/ml],while MMP-1[21.70(12.20,30.45)ng/ml vs.10.60(7.65,16.25)ng/ml],MMP-2[701.00(620.50,846.00)ng/ml vs.912.00(779.00,1100.00)ng/ml],MMP-9[6.80(2.00,10.30)ng/ml vs.21.60(10.70,66.50)ng/ml]was significantly higher than that in control group(P<0.05).The area under ROC curve of serum SAP,MMP-1,MMP-2 and MMP-9 before radiotherapy to predict RILI after SBRT were 0.881,0.784,0.760 and 0.885,respectively.Compared with before SBRT,the serum SAP level[23.42(17.27,28.57)μg/ml vs.30.09(23.51,39.86)μg/ml]was significantly increased after SBRT,while the levels of MMP-1[13.10(8.30,21.70)ng/ml vs.10.50(7.00,16.80)ng/ml],MMP-2[757.00(660.00,880.00)ng/ml vs.690.00(604.00,810.00)ng/ml]and MMP-9[6.60(2.40,17.20)ng/ml vs.2.00(2.80,3.40)ng/ml]were significantly decreased(P<0.05).In the 75 cases,63 cases(84.00%)died and 12 cases(16.00%)survived.Univariate and multivariate COX regression analysis showed that serum SAP and MMP-1,MMP-2 and MMP-9 before radiotherapy were independent influencing factors of PFS,OS and DMFS(P<0.05),and serum SAP and MMP-9 before radiotherapy were also independent influencing factors of LPFS(P<0.05).In Kaplan-Meier analysis,patients with low SAP and high MMPs had lower PFS and OS rates and shorter median PFS and OS times compared to patients with high SAP and low MMPs before radiotherapy(P<0.05).In the combined risk model of serum SAP and MMPs before radiotherapy,high-risk patients had lower PFS and OS rates and shorter median PFS and OS times compared with low-risk patients(P<0.05).Conclusion Low SAP and high MMPs levels before radiotherapy are associated with a higher risk of RILI and poor prognosis after SBRT 21 cases with RIKI were divided into observation group and 54 cases without RILIum were divided into control group.Serum SAP and MMPs before radiotherapy are promising biomarkers for early prediction of RILI and poor prognosis after SBRT in lung cancer patients.
作者
井发红
李丽娜
高婷
高艳梅
杨楠
李卓
慕玉东
Jing Fahong;Li Lina;Gao Ting;Gao Yanmei;Yang Nan;Li Zhuo;Mu Yudong(Department of Clinical Laboratory,The First Affiliated Hospital of Xi′an Medical University,Xi′an 710077,China;Department of Medical Oncology,Shaanxi Cancer Hospital,Xi′an 710077,China;Department of Radiotherapy,Shaanxi Cancer Hospital,Xi′an 710077,China;Department of Clinical Laboratory,Shaanxi Cancer Hospital,Xi′an 710077,China)
出处
《中华肺部疾病杂志（电子版）》
2024年第5期707-713,共7页
Chinese Journal of Lung Diseases(Electronic Edition)
基金
陕西卫生健康科研项目(2022B011)。
关键词
支气管肺癌
立体定向放疗
血清淀粉样蛋白P
基质金属蛋白酶
放射性肺损伤
Bronchogenic carcinoma
Stereotactic body radiation therapy
Serum amyloid P
Matrix metalloproteinases
Radiation-induced lung injury
作者简介
通信作者:李卓,Email:lizhuo721@163.com。
