|本期目录/Table of Contents|

[1]邸立君,刘 洋,孙 媛,等.脑源性无细胞DNA对肺癌并发脑转移放射性脑损伤的预测意义[J].中华肺部疾病杂志,2025,(01):80-85.[doi:10.3877/cma.j.issn.1674-6902.2025.01.013 ]
 Di Lijun,Liu Yang,Sun Yuan,et al.Significance of brain-derived cell-free DNA in predicting radiation brain injury in lung cancer with brain metastasis[J].,2025,(01):80-85.[doi:10.3877/cma.j.issn.1674-6902.2025.01.013 ]
点击复制

脑源性无细胞DNA对肺癌并发脑转移放射性脑损伤的预测意义(PDF)

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

卷:
期数:
2025年01期
页码:
80-85
栏目:
论著
出版日期:
2025-02-25

文章信息/Info

Title:
Significance of brain-derived cell-free DNA in predicting radiation brain injury in lung cancer with brain metastasis
作者:
邸立君刘 洋孙 媛李 晖
041000 临汾,临汾市人民医院肿瘤科
Author(s):
Di Lijun Liu Yang Sun Yuan Li Hui.
Department of Oncology, Linfen People's Hospital, Linfen 041000, China
关键词:
支气管肺癌 脑源性循环游离DNA 放射性脑损伤 脑转移
Keywords:
Bronchogenic carcinoma Brain-derived circulating free DNA Radiation brain injury Brain metastasis
分类号:
R734.2
DOI:
10.3877/cma.j.issn.1674-6902.2025.01.013
摘要:
目的 分析脑源性无细胞DNA(brain-derived cell-free DNA, bd-cfDNA)对肺癌脑转移放射性脑损伤(radiation brain injury, RBI)的预测意义。 方法 选择2020年3月至2022年3月我院收治的晚期肺癌并发脑转移患者83例为对象,放疗后发生RBI 33例为观察组,未发生RBI 50例为对照组。放疗前后检测血浆中总cfDNA水平,采用组织特异性甲基化模式溯源cfDNA。应用多因素二元Logistic和受试者工作特征(receiver operating characteristic, ROC)曲线分析bd-cfDNA对RBI的预测。 结果 观察组放疗后血小板淋巴细胞比值(platelet lymphocyte ratio, PLR)256.00(226.50,289.00)和总靶体积(gross tumor volume, GTV)Dmax 5 032.10(4 936.25,5 125.35)高于对照组PLR 221.50(184.25,252.25)和GTV Dmax 4 938.50(4 833.40,5 032.93)(P<0.05)。两组放疗前cfDNA差异无统计学意义(P>0.05),两组放疗后少突胶质细胞来源ΔcfDNA、神经元来源ΔcfDNA、星形胶质细胞来源ΔcfDNA及Δ总bd-cfDNA升高(P<0.05),观察组放疗后少突胶质细胞来源ΔcfDNA12.07(0.28,2 706.43)copies/ml、神经元来源ΔcfDNA11.88(1.44,4 394.05)copies/ml、星形胶质细胞来源ΔcfDNA295.84(5.63,7 407.56)copies/ml及Δ总bd-cfDNA8433.13(348.75,29 514.12)copies/ml高于对照组2.95(0.01,16.90)copies/ml、3.48(0.52,22.54)copies/ml、13.69(2.07,89.33)copies/ml、72.38(25.44,1 343.92)copies/ml(P<0.001)。观察组放疗前后少突胶质细胞来源ΔcfDNA19.80(0.25,3159.96)copies/ml、神经元来源ΔcfDNA19.61(0.48,4 646.08)copies/ml、星形胶质细胞来源ΔcfDNA262.05(1.62,8 298.91)copies/ml及Δ总bd-cfDNA 4 936.47(229.22,24 740.52)copies/ml高于对照组0.65(-0.11,14.54)copies/ml、1.63(0.07,15.45)copies/ml、3.93(-2.25,77.83)copies/ml、34.71(0.57,433.65)copies/ml(P<0.05)。多因素二元Logistic分析显示,放疗后Δ总bd-cfDNA≥568.68 copies/ml增加RBI发生风险[HR:5.194(95%CI:1.760~15.326),P=0.003]。ROC曲线分析显示,放疗后Δ总bd-cfDNA预测RBI的曲线下面积为0.782(95%CI:0.674~0.891)(P<0.05)。 结论 放疗后bd-cfDNA可预测肺癌脑转移RBI,具有临床意义。
Abstract:
Objective To analyze the predictive value of brain-derived cell-free DNA(bd-cfDNA)for radiation brain injury(RBI)in patients with lung cancer brain metastases. Methods A total of 83 patients with advanced lung cancer complicated with brain metastasis admitted to our hospital from March 2020 to March 2022 were selected as the subjects, 33 patients with RBI after brain radiotherapy were selected as the observation group, and 50 patients without RBI were selected as the control group. The total cfDNA levels in plasma were measured before and after radiotherapy, and the origin of cfDNA was traced using tissue-specific methylation patterns. Multivariate binary Logistic and receiver operating characteristic(ROC)curve were used to analyze the prediction of RBI by bd-cfDNA. Results After radiotherapy, PLR 256.00(226.50, 289.00)and GTV Dmax 5 032.10(4 936.25, 5 125.35)in observation group were higher than those in control group 252.25(221.50, 184.25)and GTV Dmax 4 938.50(4 833.40, 5 032.93)(P<0.05). There was no significant difference in cfDNA between the two groups before radiotherapy(P>0.05). After radiotherapy, cfDNA from oligodendrocytes, cfDNA from neurons, cfDNA from astrocytes and total bd-cfDNA were increased between the two groups(P<0.05). In the observation group, after radiotherapy, the source of oligodendrocytes was 12.07(0.28, 2 706.43)copies/ml, the source of neurons was 11.88(1.44, 4 394.05)copies/ml, and the source of astrocytes was cfDNA295.84(5.63, 5.28, 4 394.05)copies/ml and total bd-cfDNA 8 433.13(348.75, 29 514.12)copies/ml were higher than those in the control group 2.95(0.01, 16.90)copies/ml, 3.48(0.52, 22.54)copies/ml,13.69(2.07,89.33)copies/ml,72.38(25.44,1343.92)copies/ml(P<0.001). In the observation group before and after radiotherapy, oligodendrocyte sources were cfDNA19.80(0.25, 3 159.96)copies/ml, neuronal sources ΔcfDNA19.61(0.48, 4 646.08)copies/ml, astrocyte sources ΔcfDNA 262.05(1.62, 8 298.91)copies/ml and Δ total bd-cfDNA 4 936.47(229.22, 24 740.52)copies/ml were higher than that of the control group 0.65(-0.11, 14.54)copies/ml, 1.63(0.07, 0.07)copies/ml. 15.45)copies/ml, 3.93(-2.25, 77.83)copies/ml, 34.71(0.57, 433.65)copies/ml(P<0.05). Multivariate binary Logistic analysis showed that total bd-cfDNA≥568.68 copies/ml after radiotherapy increased the risk of RBI [HR: 5.194(95%CI: 1.760-15.326), P=0.003]. ROC curve analysis showed that the area under the curve of total bd-cfDNA predicting RBI after radiotherapy was 0.782(95%CI: 0.674-0.891)(P<0.05). Conclusion bd-cfDNA can predict RBI of lung cancer brain metastases after radiotherapy, which has clinical significance.

参考文献/References:

1 Rybarczyk-Kasiuchnicz A, Ramlau R, Stencel K. Treatment of brain metastases of non-small cell lung carcinoma[J]. Int J Mol Sci, 2021, 22(2): 593.
2 蔡定钦,孙建国,陈旭.外泌体非编码RNAs与肺癌放射治疗的研究进展[J].中华肺部疾病杂志(电子版),2024,17(4):655-658.
3 曾丽晶, 夏 煌, 陈钰昕, 等. 放射性脑损伤的研究进展[J]. 中华放射医学与防护杂志, 2024, 44(1): 65-71.
4 Turnquist C, Harris BT, Harris CC. Radiation-induced brain injury: current concepts and therapeutic strategies targeting neuroinflammation[J]. Neurooncol Adv, 2020, 2(1): vdaa057.
5 Liu APY, Smith KS, Kumar R, et al. Serial assessment of measurable residual disease in medulloblastoma liquid biopsies[J]. Cancer Cell, 2021, 39(11): 1519-1530.e4.
6 Kayhanian S, Glynos A, Mair R, et al. Cell-Free Mitochondrial DNA in Acute Brain Injury[J]. Neurotrauma Rep, 2022, 3(1): 415-420.
7 De Mattos-Arruda L, Mayor R, Ng CKY, et al. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma[J]. Nat Commun, 2015, 6: 8839.
8 Zhang B, Lian Z, Zhong L, et al. Machine-learning based MRI radiomics models for early detection of radiation-induced brain injury in nasopharyngeal carcinoma[J]. BMC Cancer, 2020, 20(1): 502.
9 郭丽娜, 王宏伟. 联合免疫检查点抑制剂治疗驱动基因阴性非小细胞肺癌脑转移的研究进展[J]. 中国肿瘤临床, 2024, 51(3): 153-158.
10 Li H, Harrison EB, Li H, et al. Targeting brain lesions of non-small cell lung cancer by enhancing CCL2-mediated CAR-T cell migration[J]. Nat Commun, 2022, 13(1): 2154.
11 Lamba N, Wen PY, Aizer AA. Epidemiology of brain metastases and leptomeningeal disease[J]. Neuro Oncol, 2021, 23(9): 1447-1456.
12 Sperduto PW, Mesko S, Li J, et al. Survival in patients with brain metastases: summary report on the updated diagnosis-specific graded prognostic assessment and definition of the eligibility quotient[J]. J Clin Oncol, 2020, 38(32): 3773-3784.
13 Smyth EN, John J, Tiu RV, et al. Clinicogenomic factors and treatment patterns among patients with advanced non-small cell lung cancer with or without brain metastases in the United States[J]. Oncologist, 2023, 28(11): e1075-e1091.
14 Ye Z, Wang J, Shi W, et al. Reprimo(RPRM)as a Potential preventive and therapeutic target for radiation-induced brain injury via multiple mechanisms[J]. Int J Mol Sci, 2023, 24(23): 17055.
15 García-Pardo M, Makarem M, Li JJN, et al. Integrating circulating-free DNA(cfDNA)analysis into clinical practice: opportunities and challenges[J]. Br J Cancer, 2022, 127(4): 592-602.
16 Southwood D, Singh S, Chatterton Z. Brain-derived cell-free DNA[J]. Neural Regen Res, 2022, 17(10): 2213-2214.
17 Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics[J]. Nat Med, 2008, 14(9): 985-90.
18 Moser T, Kühberger S, Lazzeri I, et al. Bridging biological cfDNA features and machine learning approaches[J]. Trends Genet, 2023, 39(4): 285-307.
19 Pan L, McClain L, Shaw P, et al. Non-invasive epigenomic molecular phenotyping of the human brain via liquid biopsy of cerebrospinal fluid and next generation sequencing[J]. Eur J Neurosci, 2020, 52: 4536-4545.
20 李羽斌, 李晓燕. 脑脊液循环肿瘤DNA在非小细胞肺癌柔脑膜转移中的临床应用进展[J]. 中国肺癌杂志, 2024, 27(5): 376-382.
21 孙 旻, 王梓卜, 徐 运, 等. 星形胶质细胞与神经元代谢互作在缺血性脑损伤中的作用[J]. 国际脑血管病杂志, 2023, 31(9): 703-710.
22 邓 翀, 张 泉, 田 野. 大鼠早期放射性脑损伤后少突胶质细胞内Tau蛋白表达的变化特征[J]. 中华放射医学与防护杂志, 2008, 28(1): 28-31.
23 曾丽晶, 夏 煌, 陈钰昕, 等. 放射性脑损伤的研究进展[J]. 中华放射医学与防护杂志, 2024, 44(1): 65-71.
24 马 龙, 陈绍水. 放射性脑损伤发病机制及防治的研究与进展[J]. 中国医药科学, 2020, 10(2): 37-40, 50.
25 McEwen AE, Leary SES, Lockwood CM. Beyond the blood: CSF-derived cfDNA for diagnosis and characterization of CNS tumors[J]. Front Cell Dev Biol, 2020, 8: 45.
26 Qiao S, Hao Y, Cai L, et al. Prognostic value of cell-free DNA in cerebrospinal fluid from lung cancer patients with brain metastases during radiotherapy[J]. Radiat Oncol, 2023, 18(1): 50.
27 Pollard C, Aston K, Emery BR, et al. Detection of neuron-derived cfDNA in blood plasma: a new diagnostic approach for neurodegenerative conditions[J]. Front Neurol, 2023, 14: 1272960.
28 Makranz C, Lubotzky A, Zemmour H, et al. Short report: Plasma based biomarkers detect radiation induced brain injury in cancer patients treated for brain metastasis: A pilot study[J]. PLoS One, 2023, 18(11): e0285646.

备注/Memo

备注/Memo:
基金项目: 山西省卫生健康科研项目(2019039)
通信作者: 李 晖, Email: lhczj@163.com
更新日期/Last Update: 2025-02-20