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...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。展开更多
Background： The detection of solitary pulmonary nodules （SPNs） that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed t...Background： The detection of solitary pulmonary nodules （SPNs） that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography （CT） imaging results remains a significant challenge. The 2-[^18F]-fluoro-2-deoxy-D-glucose （^18F-FDG） positron emission tomography （PET）/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[^18F]-fluorothymidine （^18F-FLT） in lung cancer PET/CT imaging. Methods： The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established （n = 12）, and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values （SUVs）, and Ki-67 proliferation marker expression were investigated. Results： The cell-tracer binding ratio for the A549 cells using the ^18F-FDG was greater than the ratio using 18F-FLT （P 〈 0.05）. The Ki-67 expression showed a significant positive correlation with the ^18F-FLT binding ratio （r = 0.824, P〈 0.01）. The tumor-to-nontumor uptake ratio of ^18F-FDG imaging in xenografts was higher than that of ^18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of ^18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of ^18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of ^18F-FDG and ^18F-FLT （r = 0.658, P〈 0.05 and r = 0.724, P〈 0.01, respectively）. Conclusions： The ^18F-FDG uptake ratio is higher than that of ^18F-FLT in A549 cells at the cellular level.^18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs.展开更多
文摘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。
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81271607）, and the National Postdoctoral Science Foundation of China （No. 2015M572810）.
文摘Background： The detection of solitary pulmonary nodules （SPNs） that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography （CT） imaging results remains a significant challenge. The 2-[^18F]-fluoro-2-deoxy-D-glucose （^18F-FDG） positron emission tomography （PET）/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[^18F]-fluorothymidine （^18F-FLT） in lung cancer PET/CT imaging. Methods： The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established （n = 12）, and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values （SUVs）, and Ki-67 proliferation marker expression were investigated. Results： The cell-tracer binding ratio for the A549 cells using the ^18F-FDG was greater than the ratio using 18F-FLT （P 〈 0.05）. The Ki-67 expression showed a significant positive correlation with the ^18F-FLT binding ratio （r = 0.824, P〈 0.01）. The tumor-to-nontumor uptake ratio of ^18F-FDG imaging in xenografts was higher than that of ^18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of ^18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of ^18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of ^18F-FDG and ^18F-FLT （r = 0.658, P〈 0.05 and r = 0.724, P〈 0.01, respectively）. Conclusions： The ^18F-FDG uptake ratio is higher than that of ^18F-FLT in A549 cells at the cellular level.^18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs.
