«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

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

卷:

期数:

2024年04期

页码:

505-511

栏目:

论著

出版日期:

2024-08-25

文章信息/Info

Title:

Significance of RASSF1A and SHOX2 methylation in bronchoalveolar lavage fluid combined with radial ultrasonic features in differentiating the property of pulmonary nodules

作者:

刘锦程¹; 2; 王 斌¹; 2; 张 雯¹; 2; 张明周¹; 2; 刘 禹¹; 2; 叶东樊¹; 2; 黄赞胜¹; 2; 邱凌霄¹; 2; 卿 斌¹; 2; 王创业¹; 2; 王南博¹; 2; 王 苹¹; 2; 郭宇航¹; 2; 周培花¹; 2; 程秋霞¹; 2; 徐 智¹; 2

400037 重庆,陆军(第三)军医大学第二附属医院呼吸与危重症医学中心¹
400037 重庆,重大呼吸疾病精准诊疗与防控重庆市重点实验室²

Author(s):

Liu Jincheng¹; 2;  Wang Bin¹; 2;  Zhang Wen¹; 2;  Zhang Mingzhou¹; 2;  Liu Yu¹; 2;  Ye Dongfan¹; 2;  Huang Zansheng¹; 2;  Qiu Lingxiao¹; 2;  Qing Bin¹; 2;  Wang Chuangye¹; 2;  Wang Nanbo¹; 2;  Wang Ping¹; 2;  Guo Yuhang¹; 2;  Zhou Peihua¹; 2;  Cheng Qiuxia¹; 2;  Xu Zhi¹; 2.

¹Department of Respiratory and Critical Care Medical Center, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China; ²Chongqing Key Laboratory for Precise Diagnosis, Treatment, Prevention and Control of Major Respiratory Diseases, Chongqing 400037, China

关键词:

肺结节;  肺泡灌洗液;  大鼠肉瘤相关区域家族1A基因甲基化;  矮小同源盒基因甲基化;  径向超声特征

Keywords:

Pulmonary nodule;  Bronchoalveolar lavage fluid;  Ras association family 1 isoform A methylation;  Short stature homeobox 2 methylation;  Radial ultrasound features

分类号:

R563

DOI:

10.3877/cma.j.issn.1674-6902.2024.04.001

摘要:

目的 分析检测肺泡灌洗液中大鼠肉瘤(rat sarcoma, Ras)相关区域家族1A基因(Ras association family 1 isoform A, RASSF1A)和矮小同源盒基因2(short stature homeobox 2, SHOX2)甲基化联合径向超声特征对肺结节性质鉴别诊断的意义。方法 选择2022年9月至2024年3月我院收治的肺结节患者90例,经组织病理学确诊恶性肺结节54例为观察组,良性肺结节36例为对照组,收集肺泡灌洗液进行细胞学检查及RASSF1A、SHOX2基因甲基化检测,比较两组甲基化阳性率,分析肺泡灌洗液甲基化检测对肺结节性质的灵敏度和特异性,采用Logistic回归分析从临床特征、径向超声特征及甲基化指标中筛选预测因子,构建恶性肺结节预测模型。结果 观察组RASSF1A阳性22例(40.74%)高于对照组1例(2.78%)(P<0.01)、SHOX2阳性25例(46.30%)高于对照组2例(5.56%)(P<0.01)、RASSF1A及SHOX2两者阳性14例(25.93%)高于对照组1例(2.78%)(P<0.05)、RASSF1A或SHOX2阳性33例(61.11%)高于对照组2例(5.56%)(P<0.01); RASSF1A或SHOX2阳性诊断恶性肺结节的灵敏度61.11%、特异性94.44%。RASSF1A或SHOX2阳性33例(61.11%)高于肺泡灌洗液细胞学阳性17例(31.48%)(P<0.05); RASSF1A或SHOX2阳性联合肺泡灌洗液细胞学阳性率72.22%; 观察组径向超声特征中边缘连续比率81.40%、内部回声不均匀比率83.72%及低回声影比率72.09%高于对照组40.00%、40.00%、45.71%(P<0.05); 多因素Logistic回归分析显示,两基因甲基化、径向超声特征边缘连续及内部回声不均匀为预测恶性肺结节的危险因素,绘制受试者工作特征曲线下面积(area under the curve, AUC)为0.886。结论 RASSF1A联合SHOX2甲基化检测肺泡灌洗液用于恶性肺结节诊断具有价值,RASSF1A及SHOX2甲基化联合径向超声特征对肺结节性质鉴别诊断有临床意义。

Abstract:

Objective To analyse the significance of methylation test of Ras association family 1 isoform A(RASSF1A)and short stature homeobox 2(SHOX2)in bronchoalveolar lavage fluid(BALF)combined with radial ultrasonic features in the differential diagnosis between malignant and benign pulmonary nodules. Methods Ninety patients with pulmonary nodules admitted to our hospital from September 2022 to March 2024 were selected, 54 cases of malignant pulmonary nodules diagnosed by histopathology were in the observation group, and 36 cases of benign pulmonary nodules were in the control group, and BALF was collected for cytological examination and methylation detection of the RASSF1A and SHOX2 genes to compare the methylation positivity rate of the two groups and analyse the sensitivity and specificity of pulmonary nodules. Logistic regression analysis was used to screen some clinical characteristics,radial ultrasonic features and methylation indexes as predictors to construct a prediction model of pulmonary nodules. Results In the observation group, 22 cases(40.74%)of RASSF1A positivity were higher than 1 case(2.78%)in the control group(P<0.01); 25 cases(46.30%)of SHOX2 positivity were higher than 2 cases(5.56%)in the control group(P<0.01); 14 cases(25.93%)of both RASSF1A and SHOX2 positivity were higher than 1 case(2.78%)in the control group(P<0.05); 33 cases(61.11%)of RASSF1A or SHOX2 positivity were higher than 2 cases(5.56%)in the control group(P<0.01; The sensitivity for diagnosing malignant lung nodules was 61.11% and the specificity was 94.44% for the positivity of RASSF1A or SHOX2. 33 cases(61.11%)of RASSF1A or SHOX2 positivity were significantly higher than 17 cases(31.48%)of BALF cytology positivity(P<0.05); Radial ultrasound characteristics of the observation group in the ratio of the continuous margins of 81.40%, the ratio of the uneven internal echo of 83.72% and the ratio of hypoechogenic shadows of 72.09% were higher than that of the control group of 40.00%, 40.00%, 45.71%(P<0.05); Multifactorial logistic regression analysis showed that two-gene methylation, continuous margins and uneven internal echo were the risk factors for predicting malignant lung nodules, and the area under the curve(AUC)of the working characteristics of the subjects was 0.886. Conclusion RASSF1A combined with SHOX2 methylation detection of BALF is valuable for the diagnosis of malignant lung nodules, and RASSF1A and SHOX2 methylation combined with radial ultrasound features are clinically relevant for the differential diagnosis of the property of lung nodules.

参考文献/References:

1 吴国明, 钱桂生. 非小细胞肺癌靶向治疗研究进展及新理念[J/CD]. 中华肺部疾病杂志(电子版), 2019, 12(4): 405-408.
2 赫 捷, 李 霓, 陈万青, 等. 中国肺癌筛查与早诊早治指南(2021,北京)[J]. 中国肿瘤, 2021, 30(2): 81-111.
3 中华医学会呼吸病学分会. 早期肺癌诊断中国专家共识(2023年版)[J]. 中华结核和呼吸杂志, 2023, 46(1): 1-18.
4 Mazzone PJ, Lam L. Evaluating the patient with a pulmonary nodule: A review[J]. JAMA, 2022, 327(3): 264-273.
5 邹明珠, 蓝博文, 林观兰, 等. 螺旋CT形态学特征在肺结节良恶性诊断中的临床意义[J/CD]. 中华肺部疾病杂志(电子版), 2023, 16(5): 729-730.
6 李 强. 螺旋CT动态增强扫描在孤立性肺结节良恶性鉴别诊断中的应用探讨[J]. 中国现代药物应用, 2024, 18(11): 75-78.
7 Pan H, Renaud L, Chaligne R, et al. Discovery of candidate DNA methylation cancer driver genes[J]. Cancer Discov, 2021,11(9): 2266-2281.
8 Li P, Liu S, Du L, et al. Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer[J]. Clin Epigenetics, 2022,14(1): 118.
9 Bin Y, Ding Y, Xiao W, et al. RASSF1A: A promising target for the diagnosis and treatment of cancer[J]. Clin Chim Acta, 2020, 504: 98-108.
10 Li N, Zeng Y, Huang J. Signaling pathways and clinical application of RASSF1A and SHOX2 in lung cancer[J]. J Cancer Res Clin Oncol, 2020, 146(6): 1379-1393.
11 Ren M, Wang C, Sheng D, et al. Methylation analysis of SHOX2 and RASSF1A in bronchoalveolar lavage fluid for early lung cancer diagnosis[J]. Ann Diagn Pathol, 2017, 27: 57-61.
12 Hutchinson BD, Shroff GS, Truong MT, et al. Spectrum of Lung Adenocarcinoma[J]. Semin Ultrasound CT MR, 2019, 40(3): 255-264.
13 Kalchiem-Dekel O, Connolly JG, Lin IH, et al. Shape-sensing robotic-assisted bronchoscopy in the diagnosis of pulmonary parenchymal lesions[J]. Chest, 2022, 161(2): 572-582.
14 Nadig TR, Thomas N, Nietert PJ, et al. Guided bronchoscopy for the evaluation of pulmonary lesions: An updated Meta-analysis[J]. Chest, 2023, 163(6): 1589-1598.
15 Zhong Q, Wang Y, Liang C, et al. Combined methylation of SHOX2 and RASSF1A genes in fiagnosing malignant pleural effusion[J]. Discov Med, 2023, 35(178): 845-852.
16 Lu H, Lin D. Diagnostic value of exfoliated tumor cells combined with DNA methylation in bronchoalveolar lavage fluid for lung cancer[J]. Medicine(Baltimore), 2023, 102(36): 1-6.
17 Shi J, Chen X, Zhang L, et al. Performance evaluation of SHOX2 and RASSF1A methylation for the aid in diagnosis of lung cancer based on the analysis of FFPE specimen[J]. Front Oncol, 2020, 10: 1-6.
18 Domagala-Kulawik J. The relevance of bronchoalveolar lavage fluid analysis for lung cancer patients[J]. Expert Rev Respir Med, 2020, 14(3): 329-337.
19 朱东平, 李海峰, 冯俊飞, 等. 肺部结节或肿块患者肺泡灌洗液SHOX2和RASSF1A基因甲基化在肺癌诊断中的价值[J]. 昆明医科大学学报, 2024, 45(3): 106-111.
20 陈瑞英, 刘 雅, 孙 婷, 等. 支气管肺泡灌洗液中SHOX2和RASSF1A基因甲基化检测对肺癌的诊断价值[J]. 郑州大学学报(医学版), 2019, 54(5): 732-736.
21 Ma S, Yu X, Jin X, et al. The usefulness of liquid-based cytology of bronchoalveolar lavage fluid combined with bronchial brush specimens in lung cancer diagnosis[J]. J Int Med Res, 2022, 50(11): 1-6.
22 王 斌, 王 静, 黄赞胜, 等. 肺超声可视化支气管肺泡灌洗在肺外周病灶诊断中的应用[J/CD]. 中华肺部疾病杂志(电子版), 2023, 16(4): 466-470.
23 Zheng X, Wang L, Chen J, et al. Diagnostic value of radial endobronchial ultrasonographic features in predominant solid peripheral pulmonary lesions[J]. J Thorac Dis, 2020, 12(12): 7656-7665.
24 Choi J, Zo S, Kim JH, et al. Nondiagnostic, radial-probe endobronchial ultrasound-guided biopsy for peripheral lung lesions: The added value of radiomics from ultrasound imaging for predicting malignancy[J]. Thorac Cancer, 2023, 14(2): 177-185.
25 何正强, 傅应云, 李亚珍, 等. 支气管腔内超声特征对肺部结节良恶性的预测价值[J]. 国际呼吸杂志, 2018(22): 1703-1707.
26 Kurimoto N, Murayama M, Yoshioka S, et al. Analysis of the internal structure of peripheral pulmonary lesions using endobronchial ultrasonography[J]. Chest, 2002, 122(6): 1887-1894.
27 王 慧, 魏美慧, 张晓菊. 提高以磨玻璃结节为表现的早期肺癌诊治水平[J]. 结核与肺部疾病杂志, 2021, 2(3): 193-196.
28 Li T, Liu Y, Zhang W, et al. A rapid liquid biopsy of lung cancer by separation and detection of exfoliated tumor cells from bronchoalveolar lavage fluid with a dual-layer“PERFECT” filter system[J]. Theranostics, 2020, 10(14): 6517-6529.
29 Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68: 394-424.
30 Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines[J]. Chest, 2013, 143: e211S-e50S.

备注/Memo

备注/Memo:

基金项目: 重庆市技术创新与应用发展专项重点项目(CSTC2021jscx-gksb-N0029)
通信作者: 徐 智, Email: xuzhihxk@tmmu.edu.cn

常用功能

更新日期/Last Update: 2024-08-25