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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2024年05期

页码:

707-713

栏目:

论著

出版日期:

2024-10-25

文章信息/Info

Title:

Expression and clinical significance of serum SAP and MMPs in lung cancer treated by stereotactic radiotherapy

作者:

井发红¹; 李丽娜²; 高 婷¹; 高艳梅³; 杨 楠¹; 李 卓¹; 慕玉东⁴

710077 西安,西安医学院第一附属医院检验科¹
710077 西安,陕西省肿瘤医院肿瘤内科²
710077 西安,陕西省肿瘤医院放疗科³
710077 西安,陕西省肿瘤医院检验科⁴

Author(s):

Jing Fahong¹;  Li Lina²;  Gao Ting¹;  Gao Yanmei³;  Yang Nan¹;  Li Zhuo¹;  Mu Yudong⁴.

¹Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, China; ²Department of Medical Oncology, Shaanxi Cancer Hospital, Xi'an 710077, China; ³Department of Radiotherapy, Shaanxi Cancer Hospital, Xi'an 710077, China; ⁴Department of Clinical Laboratory, Shaanxi Cancer Hospital, Xi'an 710077, ChinA

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

Keywords:

Bronchogenic carcinoma;  Stereotactic body radiation therapy;  Serum amyloid P;  Matrix metalloproteinases;  Radiation-induced lung injury

分类号:

R734.2

DOI:

10.3877/cma.j.issn.1674-6902.2024.05.007

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-2 701.00(620.50,846.00)ng/ml、MMP-9 6.80(2.00,10.30)ng/ml高于对照组MMP-110.60(7.65,16.25)ng/ml、MMP-2 912.00(779.00,1 100.00)ng/ml、MMP-9 21.60(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-2 757.00(660.00,880.00)ng/ml、MMP-9 6.60(2.40,17.20)ng/ml较SBRT后10.50(7.00,16.80)ng/ml、MMP-2 690.00(604.00,810.00)ng/ml、MMP-9 2.00(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。

Abstract:

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, 1 100.00)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.

参考文献/References:

1 余 璐, 李俊毅, 高苗苗, 等. 早期非小细胞肺癌患者立体定向放射治疗的预后分析[J]. 中国肺癌杂志, 2023, 26(4): 274-280.
2 Kocak Uzel E, Bagci Kilic M, Morcali H, et al. Stereotactic body radiation therapy for stage I medically operable non-small cell lung cancer[J]. Sci Rep, 2023, 13(1): 10384-10391.
3 Shan J, Xie X, Gu B, et al. Inflammation index predicts radiation-induced lung injury and prognosis in lung tumors treated with stereotactic body radiation therapy[J]. Jpn J Radiol, 2024, 42(1): 102-108.
4 Yan Y, Fu J, Kowalchuk RO, et al. Exploration of radiation-induced lung injury, from mechanism to treatment: a narrative review[J]. Transl Lung Cancer Res. 2022, 11(2): 307-322.
5 Doni A, Parente R, Laface I, et al. Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus[J]. Nat Commun. 2021, 12(1): 3739-3752.
6 Colceriu MC, Aldea PL, Rǎchişan AL, et al. Vesicoureteral reflux and innate immune system: Physiology, physiopathology, and clinical aspects[J]. J Clin Med, 2023, 12(6): 2380-2399.
7 Cheng P, Li S, Chen H. Macrophages in lung injury, repair, and fibrosis[J]. Cells, 2021, 10(2): 436-451.
8 Zhao J, Chi A, Mao R, et al. Serum amyloid p-component level may be a biomarker for lung toxicities and overall survival after thoracic radiotherapy for non-small cell lung cancer[J].Clin Laborat, 2016, 62(11): 2183-2190.
9 Di Noia V, D'Argento E, Pilotto S, et al. Blood serum amyloid A as potential biomarker of pembrolizumab efficacy for patients affected by advanced non-small cell lung cancer overexpressing PD-L1: results of the exploratory “FoRECATT” study[J]. Cancer Immunol Immunother, 2021, 70: 1583-1592.
10 Shimoda M, Ohtsuka T, Okada Y, et al. Stromal metalloproteinases: Crucial contributors to the tumor microenvironment[J]. Pathol Internat, 2021, 71(1): 1-14.
11 Olivares-Urbano MA, Griñán-Lisón C, Zurita M, et al. Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study[J]. J Cell Mol Med, 2020, 24(1): 139-148.
12 Fornieles G, Núñez MI, Expósito J. Matrix metalloproteinases and their inhibitors as potential prognostic biomarkers in head and neck cancer after radiotherapy[J]. Int J Mol Sci, 2023, 25(1): 527-538.
13 Itonaga T, Sugahara S, Mikami R, et al. Evaluation of the relationship between the range of radiation-induced lung injury on CT images after IMRT for stage I lung cancer and dosimetric parameters[J]. Ann Med, 2021, 53(1): 267-273.
14 Chen Z, Wang B, Wu Z, et al. The occurrence and development of radiation-induced lung injury after interstitial brachytherapy and stereotactic radiotherapy in SD rats[J]. J Inflammat, 2023, 20(1): 23-33.
15 Türkkan G, Willems Y, Hendriks LEL, et al. Idiopathic pulmonary fibrosis: Current knowledge, future perspectives and its importance in radiation oncology[J]. Radioth Oncol, 2021, 155: 269-277.
16 Singhal A, Kumar S. Neutrophil and remnant clearance in immunity and inflammation[J]. Immunol, 2022, 165(1): 22-43.
17 Chen W, Karhadkar TR, Ryu C, et al. Reduced sialylation and bioactivity of the antifibrotic protein serum amyloid P in the sera of patients with idiopathic pulmonary fibrosis[J]. Immunohorizons, 2020, 4(6): 352-362.
18 Shirai K, Hikita H, Sakane S, et al. Serum amyloid P component and pro-platelet basic protein in extracellular vesicles or serum are novel markers of liver fibrosis in chronic hepatitis C patients[J]. PLoS One, 2022, 17(7): e0271020.
19 Karhadkar T R, Pilling D, Gomer RH. Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice[J]. PloS one, 2021, 16(1): e0245924.
20 Peng Z, Konai MM, Avila-Cobian LF, et al. MMP-1 and adam10 as targets for therapeutic intervention in idiopathic pulmonary fibrosis[J]. ACS Pharmacol Transl Sci, 2022, 5(8): 548-554.
21 杨晓兰, 孙 莉, 胡永波, 等. 特发性肺纤维化患者支气管肺泡灌洗液及血清可溶性细胞黏附分子-1、基质金属蛋白酶-2表达水平及临床意义[J]. 实用医院临床杂志, 2022, 19(5): 178-181.
22 Stansborough RL, Al-Dasooqi N, Bateman EH, et al. Matrix metalloproteinase expression is altered in the small and large intestine following fractionated radiation in vivo[J]. Support Care Cancer, 2018, 26(11): 3873-3882.
23 梁春梅, 丁国伟, 李永友. 血清MMP-9和SAA水平对非小细胞肺癌胸部放射治疗后重症放射性肺炎合并肺部感染的预测价值[J]. 中华医院感染学杂志, 2023, 33(13): 1940-1943.
24 何明森, 何 伟, 李 刚, 等. TIMP-1、MMP-9、IL-6、PCT在重症肺炎患儿中的表达及与肺功能的关系[J]. 国际检验医学杂志, 2023, 44(9): 1121-1124.
25 Todd JL, Vinisko R, Liu Y, et al. Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort[J]. BMC Pulm Med, 2020, 20(1): 64-74.
26 钱小卫, 丁海兵, 游继军, 等. 微小miR水平联合检测在非小细胞肺癌转移中的意义[J/CD]. 中华肺部疾病杂志(电子版), 2023, 16(1): 47-50.
27 杨忠信, 李晓宇, 陈 涛, 等. IL-8和MMP-2在非小细胞肺癌患者胸腔镜肺段切除术预后评估中的价值[J]. 检验医学, 2023, 38(4): 342-346.
28 赵天源, 张艳敏, 常延河. 非小细胞肺癌组织中HAb18G、MMP-9和MMP-2表达与预后的相关性[J]. 临床与实验病理学杂志, 2020, 36(7): 819-822.
29 Zhang H, Zhao B, Zhai ZG, et al. Expression and clinical significance of MMP-9 and P53 in lung cancer[J]. Eur Rev Med Pharmacol Sci, 2021, 25(3): 1358-1365.
30 李 哲, 高敬华, 李永生, 等. 阿帕替尼联合放化疗不能切除小细胞肺癌的临床疗效[J/CD]. 中华肺部疾病杂志(电子版), 2023, 16(3): 352-354.

备注/Memo

备注/Memo:

基金项目: 陕西卫生健康科研项目(2022B011)
通信作者: 李 卓, Email: lizhuo721@163.com

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更新日期/Last Update: 2024-10-25