肺磨玻璃结节高分辨率CT影像特征及其与血管内皮生长因子、Ki-67、p53的相关性研究

High resolution CT imaging features of pulmonary ground-glass nodules and their correlation with vascular endothelial growth factor, Ki-67, p53

  • 摘要:
    目的 探讨肺磨玻璃结节(GGN)高分辨率CT(HRCT)影像特征及其与免疫组织化学(IHC)检查指标的相关性,评估其对临床的应用价值。
    方法 回顾性分析2019年1月至2020年5月于南方医科大学顺德医院(佛山市顺德区第一人民医院)经手术和组织病理学检查结果确诊的144例肺GGN患者的临床资料,其中男性46例、女性98例,年龄28~80(51.9±11.9)岁。所有患者均行手术及IHC检查,根据2021年世界卫生组织肺肿瘤组织新分类方法,将144例肺GGN患者分为浸润前病变(PI)、微浸润性腺癌(MIA)和浸润性腺癌(IA)3组,比较3组肺GGN患者HRCT影像特征的差异及其与IHC检查指标的相关性。影像特征的组间比较采用方差分析或χ2检验。采用单因素及多因素Logistic回归模型分析影响因素及建立预测模型,并绘制受试者工作特征曲线,获得最佳诊断临界值。采用χ2检验分析HRCT影像特征与IHC检查指标表达水平的相关性。
    结果 单因素Logistic回归分析结果显示,GGN长径、分叶征、毛刺征、胸膜牵拉征、瘤-肺边界、微血管穿行征、空气支气管征在3组间的差异均有统计学意义(F=8.952~82.901,均P<0.05)。多因素Logistic回归分析结果显示,GGN长径是评估肺GGN浸润性的独立危险因素。当GGN长径<6 mm时倾向于PI;当6 mm≤GGN长径≤10 mm时倾向于MIA;当GGN长径>10 mm时倾向于IA。IHC检查结果显示,血管内皮生长因子(VEGF)、p53、细胞增殖核抗原(Ki-67)对肺GGN浸润程度的预测价值较高,曲线下面积分别为0.829、0.773、0.760。相关性分析结果显示,GGN长径>10 mm、分叶征、毛刺征、胸膜牵拉征、瘤-肺边界与VEGF、p53、Ki-67的高表达水平具有相关性(χ2=13.582~41.351,均P<0.05);微血管穿行征与Ki-67的高表达和VEGF、p53的低表达水平具有相关性(χ2=15.111、15.644、16.121,均P<0.05)。
    结论 GGN长径是评估肺GGN浸润性的独立危险因素,具有较好的诊断效能。肺GGN的HRCT影像特征与Ki-67、p53和VEGF表达水平具有相关性,将肺GGN的HRCT影像特征和IHC检查指标综合分析可以有效评估组织病理学分型、肿瘤细胞的增殖活性及浸润程度,为临床对肺GGN患者的管理及选择合适的治疗方案提供有价值的参考。

     

    Abstract:
    Objective To investigate the high resolution CT (HRCT) imaging features of pulmonary ground-glass nodules (GGN) and their correlation with immunohistochemical (IHC) examination indexes and evaluate their clinical value.
    Methods The clinical data of 144 patients with pulmonary GGN diagnosed by surgery and histopathological examination in Shunde Hospital of Southern Medical University (the First People's Hospital of Shunde) from January 2019 to May 2020 were retrospectively analyzed, including 46 males and 98 females, aged 28–80 (51.9±11.9) years old. All patients underwent surgery and IHC. Based on the new classification of lung tumor tissue by the World Health Organization in 2021, 144 patients with pulmonary GGN were divided into three groups: pre-invasive lesion (PI), microinvasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA). The differences in HRCT imaging features of the three groups of pulmonary GGN patients and their correlation with IHC examination indexes were compared. The image features were compared between groups by analysis of variance or χ2 test. Univariate and multivariate Logistic regression models were used to analyze the influencing factors and establish a prediction model. In addition, the receiver operator characteristic curves were drawn to obtain the best diagnostic cut-off value. χ2 test was used to analyze the correlation between HRCT image features and the expression level of IHC examination indexes.
    Results Results of univariate Logistic regression analysis showed that the GGN diameter, lobulation, spiculation, pleural traction sign, tumor-lung boundary, microvascular perforation sign and air bronchial sign were significantly different among the three groups (F=8.952–82.901, all P<0.05). Meanwhile, the results of multivariate Logistic regression analysis showed that the GGN diameter was an independent risk factor for the evaluation of pulmonary GGN infiltration. It tended to PI when the GGN diameter was <6 mm, MIA when the GGN diameter was 6 mm≤GGN diameter≤10 mm, and IA when the GGN diameter was >10 mm. Results of IHC showed that vascular endothelial growth factor (VEGF), p53, and proliferating cell nuclear antigen (Ki-67) had high predictive values in predicting the degree of pulmonary GGN infiltration, with area under curves of 0.829, 0.773, and 0.760, respectively. Moreover, results of correlation analysis showed that patients with GGN diameter of >10 mm, lobulation, spiculation, and pleural traction sign as well as tumor-lung boundary were correlated with the expression of VEGF, p53, Ki-67 (χ2=13.582–41.351, all P<0.05). Microvascular perforation sign was correlated with the high expression level of Ki-67, and the low expression level of VEGF and p53 (χ2=15.111, 15.644, 16.121; all P<0.05).
    Conclusions GGN diameter was an independent risk factor for the evaluation of pulmonary GGN infiltration and has good diagnostic efficacy. The HRCT imaging features of the pulmonary GGN were correlated with the expression levels of Ki-67, p53, and VEGF. The comprehensive analysis of HRCT imaging features and IHC examination indexes of pulmonary GGN can evaluate the histopathological classification, proliferative activity, and infiltration of tumor cells, as well as provide valuable references for clinical management and selection of appropriate treatment for patients with pulmonary GGN.

     

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