- 作者列表："Matthiesen R
:Bronchoalveolar lavage fluid (BALF) is a lung fluid. BALF is extracted from the lungs by a bronchoscope. The first step is to instill saline liquid into the lungs followed by extraction. The extracted liquid is depleted from cells by low spin centrifugation. The biochemical content of BALF is mainly composed of phospholipids and proteins and to less extent nucleic acids (DNA, miRNA, mRNA). The proteins, mRNAs, miRNAs, and lipids mirror the pathophysiological state of the patient and are consequently regarded as a rich source of biomarkers with already some examples of established clinical applications. Recently, in Proteomics Clin. Appl. 2019, 13, 1900028, Sim et al. established a novel MS-based proteomics protocol for BALF lung cancer sample analysis by combining antibody-based depletion of high abundant BALF proteins, high pH peptide fractionation, and label free quantitation on a high resolution Orbitrap Fusion instrument. They demonstrate an improvement in BALF sample coverage compared with some previous published methodologies. Notably, the result from the study supports the hypothesis that BALF more than serum reflects the lung cancer proteome and for this reason is a promising source for lung cancer biomarkers.
: 支气管肺泡灌洗液 (BALF) 是肺液。通过支气管镜从肺提取BALF。第一步是将盐水注入肺部，然后提取。通过低自旋离心从细胞中去除提取的液体。BALF的生化成分主要由磷脂和蛋白质组成，核酸 (DNA、miRNA、mRNA) 含量较低。蛋白质、mrna、mirna和脂质反映了患者的病理生理状态，因此被认为是生物标志物的丰富来源，已经有一些临床应用的实例。最近，在蛋白质组学中的Clin。Appl。2019，13，1900028，Sim等人通过结合高丰度BALF蛋白的基于抗体的耗竭、高pH肽分级、和高分辨率Orbitrap融合仪上的无标记定量。它们证明了与以前发表的一些方法相比，BALF样品覆盖率的改善。值得注意的是，该研究的结果支持BALF比血清更多地反映肺癌蛋白质组的假设，并且因此是肺癌生物标志物的有希望的来源。
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.