[1]袁 瑞a,汪桃利b,余文辉a,等.基于临床病理特征和影像学及血清生物指标分析对肺结节性质预测模型的构建与验证[J].现代检验医学杂志,2024,39(01):146-151+157.[doi:10.3969/j.issn.1671-7414.2024.01.027]
 YUAN Ruia,WANG Taolib,YU Wenhuia,et al.Construction and Validation of A Prediction Model for Pulmonary Nodule Nature Based on Clinicopathological Features, Imaging and Serum Biomarkers[J].Journal of Modern Laboratory Medicine,2024,39(01):146-151+157.[doi:10.3969/j.issn.1671-7414.2024.01.027]
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基于临床病理特征和影像学及血清生物指标分析对肺结节性质预测模型的构建与验证()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年01期
页码:
146-151+157
栏目:
检验与临床
出版日期:
2024-01-15

文章信息/Info

Title:
Construction and Validation of A Prediction Model for Pulmonary Nodule Nature Based on Clinicopathological Features, Imaging and Serum Biomarkers
文章编号:
1671-7414(2024)01-146-07
作者:
袁 瑞a汪桃利b余文辉a张书楠a罗胜华a李运雷a王向荣c王家传d郭海涛e
(广州中医药大学第四临床医学院/ 深圳市中医院a. 检验科;b. 肿瘤科;c. 放射科;d. 病理科;e. 胸外科,广东深圳 518033)
Author(s):
YUAN Ruia WANG Taolib YU Wenhuia ZHANG Shunana LUO Shenghuaa LI Yunleia WANG Xiangrongc WANG Jiachuand GUO Haitaoe
(a. Department of Clinical Laboratory; b. Department of Oncology; c. Department of Radiology; d. Department of Pathology; e. Department of Thoracic Surgery, Shenzhen Traditional Chinese Medicine Hospital / the Fourth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Shenzhen 518033, China)
关键词:
肺结节临床病理特征影像学生物指标预测模型
分类号:
R446;R563
DOI:
10.3969/j.issn.1671-7414.2024.01.027
文献标志码:
A
摘要:
目的 基于临床病理特征和影像学及血清生物指标分析构建肺结节(pulmonary nodules, PN)性质预测模型并验证,为肺癌早诊断和早治疗提供科学决策。方法 对2019 年1 月~ 2023 年2 月深圳市中医医院胸外科和肿瘤科816例行手术切除或肺活检病理诊断明确的PN 患者进行回顾性分析。其中,剔除不符合纳入标准者113 例,余下703 例纳入研究。该研究基于PN 患者临床病理特征( 年龄、性别、吸烟史、戒烟史、癌症家族史)、胸部影像学( 结节最大直径、病变位置、边界清晰、分叶、毛刺、空泡、血管集束征、钙化、空气支气管征、肺气肿、结节性质及胸膜凹陷、结节数量)和血清癌胚抗原(carcinoembryonic antigen, CEA)、细胞角蛋白19 片段(cytokeratin 19 fragment, CYFRA21-1)、鳞状细胞癌抗原(squamous cell carcinoma antigen, SCCA),将上述病例随机分为建模组(n=552,良性237 例,恶性315 例)和验证组(n=151,良性85 例,恶性66 例)。首先,对研究对象进行单变量分析以筛选有统计学意义的PN 性质预测因子。然后,进行多变量回归分析以筛选PN 性质的独立预测因子。最后,采用logistic 回归分析构建PN 性质的预测模型。再将验证组数据分别代入该模型与梅奥诊所(Mayo clinic,Mayo)模型、退伍军人事务(veterans affairs, VA) 模型、Brock大学(Brock University, Brock)模型、北京大学(Peking University, PKU)模型和广州医科大学(Guangzhou MedicalUniversity, GZMU)模型计算PN 恶性概率,绘制受试者工作特征(receiver operating characteristic, ROC) 曲线。根据曲线下面积(area under the curve,AUC) 比较各模型的诊断效能。结果 单变量分析筛选的具有统计学意义的变量包括年龄、癌症家族史、结节最大直径、结节性质、肺上叶、钙化、血管集束征、分叶、边界清晰、毛刺以及血清CEA,SCCA,CYFRA21-1 等。多变量回归分析显示年龄、CEA,边界、CYFRA21-1,SCCA,肺上叶、结节最大直径、癌症家族史、毛刺、结节性质等为PN 恶性的独立预测因子。该研究构建的PN 性质预测模型方程如下:f(x)= ex/ (1+ex), X=(-6.3188+0.020 8 年龄+0.527 4×CEA-0.928 4× 边界+0.294 6×Cyfra21-1+0.294× 结节最大直径+1.220 1× 癌症家族史+0.5732× 肺上叶+0.064 8×SCCA +1.461 5× 毛刺 +1.497 6× 结节性质)。该模型与Mayo 模型和VA 模型比较,AUC(0.799vs 0.659,0.650) 差异具有统计学意义(Z=3.029,2.638,P=0.003,0.008)。然而,该模型与Brock 模型、PKU 模型、GZMU 模型比较,AUC(0.799 vs 0.762,0.773,0.769) 差异无统计学意义(Z=1.063,0.686, 0.757,P=0.288,0.493,0.449)。结论 该研究构建的PN 性质预测模型较为准确可靠,可帮助临床实现早诊断和早干预,值得推广应用。
Abstract:
Objective The study aimed to construct and validate a predictive model for pulmonary nodules (PN) nature based on clinicopa-thological features, imaging, and serum biomarkers, so as to provide scientificdecision-making for early diagnosis and treatment of lung cancer. Methods A retrospective was performed on 816 PN patients with definited pathological diagnosis who received surgical resection analysisor lung biopsy in the Department of Thoracic Surgery and Oncology of Shenzhen Traditional Chinese Medicine Hospital from January 2019 to February 2023. Among them, 113 cases that did not meet the inclusion criteria were excluded, and the remaining 703 cases were included in the study. The study based on the clinicopathologic features (age, gender, smoking history, smoking cessation history and family history of cancer), chest imaging (maximum diameter of nodule, location of lesion,clear border, Lobulation, spiculation, vascular convergence sign, vacuole, calcification, air bronchial sign, emphysema, nodule type and pleural indentation, nodule number) and serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCCA) in patients with PN. These cases were randomly divided into a modeling group (n=552, 237 benign, 315 malignant) and a validation group (n=151, 85 benign, 66 malignant). First, univariate analysis was performed to screen for statistically significant predictors of nodules nature. Then, multivariate regression analysis was performed to screen for independent predictors of nodules nature. Finally, the prediction model of PN nature was constructed by logistic regression analysis. Subsequently, the validation group data were entered into the proposed model and Mayo clinic (Mayo) model, veterans affairs (VA) model, Brock University (Brock) model, Peking University (PKU) model and Guangzhou Medical University (GZMU) model, respectively. PN malignancy probability was calculated. The receiver operating characteristic (ROC) curves were plotted. The diagnostic efficiency of each model was compared according to the area under the curve (AUC). Results There were statistically significant variables including age, family history of cancer, maximum nodule diameter, nodule type, upper lobe of lung, calcification, vascular convergence sign, lobulation, clear border, spiculation, and serum CEA, SCCA, CYFRA21-1 using univariate analysis. Multiple regression analysis showed that age, CEA, clear border, CYFRA21-1, SCCA, upper lobe of lung, maximum nodule diameter, family history of cancer, spiculation and nodule type were independent predictors of PN nature. The prediction model equation constructed in this study is as follows: f(x) = ex/ (1+ex), X= (-6.318 8+0.020 8×Age+0.527 4×CEA-0.928 4×clear border+0.294 6×Cyfra21- 1+0.294×maximum nodule diameter+1.220 1× family history of cancer +0.573 2× upper lobe of lung +0.064 8×SCCA +1.461 5× Spiculation +1.497 6 ×nodule type). The AUC (0.799 vs 0.659,0.650) of the proposed model was significantly higher compared with Mayo model and VA model, and there were statistically significant differences (Z=3.029, 2.638, P=0.003, 0.008). However, compared with Brock model, PKU model and GZMU model, the differences of AUC (0.799 vs 0.762, 0.773, 0.769) were not statistically significant (Z=1.063, 0.686, 0.757, P=0.288, 0.493, 0.449). Conclusion The prediction model for PN nature established in this study is accurate and reliable, which can help clinics with early diagnosis and early intervention, and this prediction model deserves to be popularized.

参考文献/References:

[1] SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA-A Cancer Journal for Clinicians, 2021, 71(3): 209-249.
[2] DE KONING H J, VAN DER AALST C M, DE JONG P A, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial[J]. New England Journal of Medicine, 2020, 382(6): 503-513.
[3] POTTER A L, ROSENSTEIN A L, KIANG M V, et al. Association of computed tomography screening with lung cancer stage shift and survival in the United States: quasi-experimental study[J]. BMJ, 2022, 376: e069008.
[4] SWENSEN S J, SILVERSTEIN M D, ILSTRUP D M, et al. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules[J]. Archives of Internal Medicine, 1997, 157(8): 849-855.
[5] GOULD M K, ANANTH L, BARNETT P G, et al. A clinical model to estimate the pretest probability of lung cancer in patients with solitary pulmonary nodules[J].Chest, 2007, 131(2): 383-388.
[6] MCWILLIAMS A, TAMMEMAGI M C, MAYO J R, et al. Probability of cancer in pulmonary nodules detected on first screening CT[J]. New England Journal of Medicine, 2013, 369(10): 910-919.
[7] 李运, 陈克终, 隋锡朝, 等. 孤立性肺结节良恶性判断数学预测模型的建立[J]. 北京大学学报(医学版), 2011, 43(3): 450-454. LI Yun, CHEN Kezhong, SUI Xichao, et al. Establishment of a mathematical prediction model to evaluate the probability of malignancy or benign in patients with solitary pulmonary nodules[J]. Journal of Peking University(Health Sciences), 2011, 43(3): 450-454.
[8] ZHANG Man, ZHUO Na, GUO Zhanlin, et al. Establishment of a mathematic model for predicting malignancy in solitary pulmonary nodules[J]. Journal of Thoracic Disease, 2015, 7(10): 1833-1841.
[9] 周清华, 范亚光, 王颖, 等. 中国肺癌低剂量螺旋CT 筛查指南(2018 年版)[J]. 中国肺癌杂志, 2018, 21(2):67-75. ZHOU Qinghua, FAN Yaguang, WANG Ying, et al. China national lung cancer screening guideline with low-dose computed tomography(2018 version)[J].Chinese Journal of Lung Cancer, 2018, 21(2): 67-75.
[10] 中华医学会呼吸病学分会肺癌学组, 中国肺癌防治联盟专家组. 肺结节诊治中国专家共识(2018 年版)[J]. 中华结核和呼吸杂志, 2018, 41(10): 763-771. Lung Cancer Group of Chinese Thoracic Society, Expert Team, Union of Chinese Lung Cancer Management. Chinese expert consensus on diagnosis and treatment in pulmonary nodules(2018 version)[J]. Chinese Journal of Tuberculosis and Respiratory Diseases, 2018, 41(10): 763-771.
[11] National Lung Screening Trial Research Team, ABERLE D R, ADAMS A M, et al. Reduced lungcancer mortality with low-dose computed tomographic screening[J]. New England Journal of Medicine, 2011, 365(5): 395-409.
[12] VAN IERSEL C A, DE KONING H J, DRAISMA G, et al. Risk-based selection from the general population in a screening trial: selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON)[J].International Journal of Cancer, 2007, 120(4): 868-874.
[13] ADAMS S J, STONE E, BALDWIN D R, et al. Lung cancer screening[J]. Lancet, 2023, 401(10374): 390-408.
[14] LEE H J, GOO J M, LEE C H, et al. Nodular groundglass opacities on thin-section CT: size change during follow-up and pathological results[J]. Korean Journal of Radiology, 2007, 8(1): 22-31.
[15] LI Wangjia, L? Fajin, TAN Yiwen, et al. Benign and malignant pulmonary part-solid nodules: differentiation via thin-section computed tomography[J]. Quantitative Imaging in Medicine and Surgery, 2022, 12(1): 699-710.
[16] ZAHARUDIN N, JAILAINI M F M, ABEED N N N, et al. Prevalence and clinical characteristics of malignant lung nodules in tuberculosis endemic area in a single tertiary centre[J]. BMC Pulmonary Medicine, 2022, 22(1): 328.
[17] KANWAL M, DING Xiaoji, CAO Yi. Familial risk for lung cancer[J]. Oncology Letters, 2017, 13(2): 535-542.
[18] ANG L, CHAN C P Y, YAU W P, et al. Association between family history of lung cancer and lung cancer risk: a systematic review and meta-analysis [J]. Lung Cancer, 2020, 148: 129-137.
[19] LARICI A R, FARCHIONE A, FRANCHI P, et al. Lung nodules:size still matters[J]. European Respiratory Review, 2017, 26(146): 170025.
[20] NOORELDEEN R, BACH H. Current and future development in lung cancer diagnosis[J]. International Journal of Molecular Sciences, 2021, 22(16): 8661.
[21] 王旋, 崔立春, 党升强. 非小细胞肺癌放化疗联合靶向治疗对血清肿瘤标志物、免疫功能及Cyclin D3水平影响的相关研究[J]. 现代检验医学杂志, 2021, 36(4): 25-30. WANG Xuan, CUI Lichun, DANG Shengqiang. Effects of radiotherapy and chemotherapy combined with targeted therapy on serum tumor markers, immune function and CyclinD3 level in non-small cell lung cancer[J]. Journal of Modern Laboratory Medicine, 2021, 36(4): 25-30.
[22] 李辉, 汪春新, 秦明明, 等. 肺癌患者血清7 项肿瘤标志物联合检测在病理分型及临床分期中的应用价值研究[J]. 现代检验医学杂志, 2021, 36(4): 5-9, 121. LI Hui, WANG Chunxin, QIN Mingming, et al. Study on the application value of combined detection of 7 tumor markers in serum of patients with lung cancer in pathological classification and clinical staging[J].Journal of Modern Laboratory Medicine, 2021, 36(4): 5-9, 121.
[23] 彭瑛, 邓正华, 温先勇. 国内13 种血清肿瘤标志物对肺癌诊断价值的Meta分析[J]. 现代检验医学杂志, 2016, 31(1): 96-100. PENG Ying, DENG Zhenghua, WEN Xianyong. Diagnostic value of thirteen types of serum tumor markers for lung cancer in China: a meta-analysis[J].Journal of Modern Laboratory Medicine, 2016, 31(1): 96-100.
[24] 中华医学会肿瘤学分会, 中华医学会杂志社. 中华医学会肺癌临床诊疗指南(2022 版)[J]. 中华医学杂志, 2022, 102(23): 1706-1740. Oncology Society of Chinese Medical Association, Chinese medical association Publishing House. Chinese medical association guideline for clinical diagnosis and treatment of lung cancer(2022 edition)[J]. National Medical Journal of China, 2022, 102(23): 1706-1740.

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备注/Memo

备注/Memo:
基金项目: 深圳市科技计划项目(JCYJ20190812180001770):β- 细辛醚调控LncRNA SNHG5/miR-205-5p/ PTEN 信号轴干预EGFRTKIs获得性耐药相关机制研究。
作者简介:袁瑞(1988-),男,硕士研究生,主管技师,临床生化检验,E-mail:13809891469@163.com。
通讯作者:余文辉(1964-),男,主任技师,硕士生导师,临床生化检验与肿瘤学研究,E-mail: whyuchina@163.com。
更新日期/Last Update: 2024-01-15