Chronic Obstructive Pulmonary Disease Quantification Using CT Texture Analysis and Densitometry: Results From the Danish Lung Cancer Screening Trial.
- 作者列表："Sørensen L","Nielsen M","Petersen J","Pedersen JH","Dirksen A","de Bruijne M
:OBJECTIVE. The purpose of this study is to establish whether texture analysis and densitometry are complementary quantitative measures of chronic obstructive pulmonary disease (COPD) in a lung cancer screening setting. MATERIALS AND METHODS. This was a retrospective study of data collected prospectively (in 2004-2010) in the Danish Lung Cancer Screening Trial. The texture score, relative area of emphysema, and percentile density were computed for 1915 baseline low-dose lung CT scans and were evaluated, both individually and in combination, for associations with lung function (i.e., forced expiratory volume in 1 second as a percentage of predicted normal [FEV1% predicted]), diagnosis of mild to severe COPD, and prediction of a rapid decline in lung function. Multivariate linear regression models with lung function as the outcome were compared using the likelihood ratio test or the Vuong test, and AUC values for diagnostic and prognostic capabilities were compared using the DeLong test. RESULTS. Texture showed a significantly stronger association with lung function (p < 0.001 vs densitometric measures), a significantly higher diagnostic AUC value (for COPD, 0.696; for Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 1, 0.648; for GOLD grade 2, 0.768; and for GOLD grade 3, 0.944; p < 0.001 vs densitometric measures), and a higher but not significantly different association with lung function decline. In addition, only texture could predict a rapid decline in lung function (AUC value, 0.538; p < 0.05 vs random guessing). The combination of texture and both densitometric measures strengthened the association with lung function and decline in lung function (p < 0.001 and p < 0.05, respectively, vs texture) but did not improve diagnostic or prognostic performance. CONCLUSION. The present study highlights texture as a promising quantitative CT measure of COPD to use alongside, or even instead of, densitometric measures. Moreover, texture may allow early detection of COPD in subjects who undergo lung cancer screening.
: 客观。本研究的目的是确定纹理分析和密度测量是否是肺癌筛查环境中慢性阻塞性肺疾病 (COPD) 的补充定量测量。材料和方法。这是一项前瞻性 (2004-2010) 在丹麦肺癌筛查试验中收集的数据的回顾性研究。对 1915 例基线低剂量肺ct扫描进行纹理评分、肺气肿相对面积和百分位密度计算，并进行单独和联合评估，对于与肺功能的关联 (i.e.，1 秒用力呼气量占预计正常值的百分比 [预计FEV1 %])，诊断轻度至重度COPD，并预测肺功能快速下降。使用似然比检验或Vuong检验比较以肺功能为结局的多变量线性回归模型，使用DeLong检验比较诊断和预后能力的AUC值。结果。纹理显示与肺功能的相关性显著更强 (与密度测量相比，p <0.001)，诊断AUC值显著更高 (对于COPD，0.696; 慢性阻塞性肺病全球倡议 (GOLD) 1 级，0.648; GOLD 2 级，0.768; GOLD 3 级，0.944;与密度测量相比，p <0.001)，并且与肺功能下降的相关性更高但无显著差异。此外，只有纹理可以预测肺功能的快速下降 (AUC值，0.538; 与随机猜测相比，p <0.05)。纹理和两种密度测量措施的组合加强了与肺功能和肺功能下降的关联 (分别为p <0.001 和p <0.05，vs纹理) 但没有改善诊断或预后性能。结论。本研究强调纹理是一种有前途的COPD定量CT测量方法，可与密度测量一起使用，甚至代替密度测量。此外，纹理可以允许在经历肺癌筛查的受试者中早期检测COPD。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.