- 作者列表："Zheng X","Sun X","Liu Q","Huang Y","Yuan Y
:Background: Previous studies have reported mixed results regarding the composition of respiratory microbiota in lung cancer patients. Therefore, relying on previously published studies, we sought to estimate the relative proportion of respiratory microbiota between lung cancer cases and controls.Methods: MEDLINE, Embase, The Cochrane Library, and Web of Science online databases were systematically searched from inception up to October 14, 2019, to retrieve relevant studies. The relative abundance of each predominant taxon of respiratory microbiota in lung cancer patients and controls was pooled using the reported outcome data.Results: A total of 8 studies comprising 530 participants were included in the final analysis. The pooled phylum level analysis revealed that Bacteroidetes and Proteobacteria were the most abundant bacterial phyla among all participants, recording 17.5%, 47.5% in lung cancer patients, 28.2%, 39.27% in patients with benign pulmonary diseases and 40.62%, 32.09% in healthy controls, respectively. In addition, Actinobacteria and Firmicutes phyla were abundant in lung cancer cases compared to other groups (14.8%, 17.62% for lung cancer versus 13.04%, 13.16% for benign pulmonary nodules and 12.43%, 12.45% for healthy controls). At genus level, Prevotella was predominant in all the participants, and its proportion was relatively lower in cancer patients (25.74% for lung cancer versus 35.59% and 36.75% for benign pulmonary nodules and healthy controls, respectively). Comparatively, Streptococcus was more abundant in lung cancer cases (9.65% in lung cancer versus 7.98%, 7.26% in benign pulmonary nodules and healthy controls).Conclusions: The respiratory microbiota composition of respiratory microbiota significantly differs between lung cancer patients and healthy individuals, and may be used as potential biomarker of lung cancer. In addition, larger sample size, standardized procedures, dynamic monitoring, metabolomics, and culturomics are needed to confirm these results.
背景: 先前的研究已经报道了关于肺癌患者呼吸道微生物群组成的混合结果。因此，依靠先前发表的研究，我们试图估计肺癌病例和对照之间呼吸微生物群的相对比例。方法: 系统检索MEDLINE、Embase、The Cochrane Library和Web of Science在线数据库，从开始至 2019 年 10 月 14 日，检索相关研究。使用报告的结局数据汇总肺癌患者和对照中呼吸系统微生物群的每个主要分类群的相对丰度。结果: 最终分析共纳入 8 项研究，包括 530 名参与者。汇集门水平分析发现，拟杆菌和变形菌是所有参与者中最丰富的细菌门，记录 17.5%，47.5% 在肺癌患者中，28.2%，良性肺部疾病患者和健康对照者分别为 39.27% 和 40.62% 、 32.09%。此外，与其他组相比，肺癌病例中放线菌和冷门菌含量丰富 (14.8%，肺癌为 17.62%，肺良性结节为 13.04%，肺良性结节为 13.16%，肺良性结节为 12.43%，12.45% 为健康对照)。在属水平上，Prevotella在所有参与者中占优势，其在癌症患者中的比例相对较低 (肺癌为 25.74%，良性肺结节和健康对照为 35.59% 和 36.75%，分别)。相比之下，链球菌在肺癌病例中更丰富 (肺癌为 9.65%，良性肺结节和健康对照为 7.98%，7.26%)。结论: 肺癌患者与健康人呼吸系统菌群组成存在显著差异，可作为肺癌的潜在生物标志物。此外，还需要更大的样本量、标准化程序、动态监测、代谢组学和培养学来证实这些结果。
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.