- 作者列表："Liu Q","Huang Y","Chen H","Liu Y","Liang R","Zeng Q
OBJECTIVE:This study aimed to determine the potential of radiomic features extracted from preoperative computed tomography to discriminate malignant from benign indeterminate small (≤10 mm) pulmonary nodules. METHODS:A total of 197 patients with 210 nodules who underwent surgical resections between January 2011 and March 2017 were analyzed. Three hundred eighty-five radiomic features were extracted from the computed tomographic images. Feature selection and data dimension reduction were performed using the Kruskal-Wallis test, Spearman correlation analysis, and principal component analysis. The random forest was used for radiomic signature building. The receiver operating characteristic curve analysis was used to evaluate the model performance. RESULTS:Fifteen principal component features were selected for modeling. The area under the curve, sensitivity, specificity, and accuracy of the prediction model were 0.877 (95% confidence interval [CI], 0.795-0.959), 81.8% (95% CI, 72.0%-90.9%), 77.4% (95% CI, 63.9%-89.3%), and 80.0% (95% CI, 72.0%-86.7%) in the validation cohort, respectively. CONCLUSIONS:Computed tomography-based radiomic features showed good discriminative power for benign and malignant indeterminate small pulmonary nodules.
目的: 本研究旨在确定从术前计算机断层扫描中提取的放射组学特征鉴别恶性和良性不确定小 (≤ 10毫米) 肺结节的潜力。 方法: 分析 2011 年 1 月至 2017 年 3 月接受手术切除的 197 例患者 210 个结节。从计算机断层图像中提取了三百八十五个放射组学特征。使用Kruskal-Wallis检验、Spearman相关分析和主成分分析进行特征选择和数据降维。随机森林用于放射组学签名构建。采用受试者工作特征曲线分析评价模型性能。 结果: 选取 15 个主成分特征进行建模。预测模型的曲线下面积、灵敏度、特异度和准确度分别为 0.877 (95% 可信区间 [CI]，0.795-0.959)，81.8% (95% CI，72.0%-90.9%)，验证队列中分别为 77.4% (95% CI，63.9%-89.3%) 和 80.0% (95% CI，72.0%-86.7%)。 结论: 基于计算机断层扫描的放射组学特征对良恶性不确定小结节显示出良好的鉴别能力。
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.