Increasing evidence suggests that numerous fork-head transcription factors are required to repress the mammalian cells phenotype. Among them, Foxk2 is a ubiquitously expressed family member, but the role of Foxk2 in mediating tumor metastasis in non-small cell lung cancer has not been explored. In this investigation reduced Foxk2 expression was found in lung adenocarcinoma tissues compared with the adjacent non-tumor tissues, and was associated with better overall survival. Low expression was also found in the NSCLC cell lines such as A549, NCI-H520, H1299, H358 and H460 cells. Recombinant lentivirus expressing Foxk2 constructs or ShFoxk2 were developed and transfected into A549 cells or NCI-H520 cells, immunofluorescence assay, qRT-PCR, and western blot analysis were used to measure the change of the epithelial markers, E-cadherin and α-catenin, and mesenchymal markers N-cadherin and vimentin. Wound healing assay and Transwell assay were used to measure the relative cell invasion ability. MTT assay, Edu assay, and cell cycle distribution analysis were used to confirm the effect of Foxk2 on cell proliferation. ChIP-seq, qChIP, as well as luciferase reporter gene assays were used to detect the target genes regulated by Foxk2, Bioinformatics predicated the potential miRNAs that could target Foxk2. Our study demonstrated that Foxk2 played major roles in NSCLC EMT by directly targeting N-cadherin and Snail, we found that Foxk2 regulated NSCLC cell growth by suppressing the expression of cyclin D1 and CDK4, which suggested that Foxk2 might be a multifunctional regulator in NSCLC. The expression of Foxk2 may be regulated by miR-1271, which could serve as a promising therapeutic target for NSCLC.

KeywordsDiagnostic yield; electromagnetic navigation bronchoscopy (ENB); peripheral pulmonary lesions (PPLs); transbronchial lung biopsy (TBLB); virtual bronchoscopic navigation (VBN). Correspondence AbstractBackground: To compare the diagnostic yield of peripheral pulmonary lesions (PPLs) with and without navigation system. Methods: Studies dating from January 1990 to October 2019 were collected from databases. Diagnostic yield of navigation bronchoscopy and non-navigation bronchoscopy was extracted from comparative studies. Subgroup analysis was adopted to test diagnostic yield variation by lesion size, lobe location of the lesion, distance from the hilum, bronchus sign and nature of the lesion. Results: In total, 2131 patients from 10 studies were enrolled into the study. Diagnostic yield of navigation bronchoscopy was statistically higher than nonnavigation bronchoscopy for PPLs (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.32, 2.18, P < 0.001), particularly for PPLs in the peripheral third lung (OR 2.26, 95% CI 1.48, 3.44, P < 0.001) and for bronchus sign positive PPLs (OR 2.26, 95% CI 1.21, 4.26, P = 0.011). Navigation bronchoscopy had better performance than non-navigation bronchoscopy when PPLs were ≤ 20 mm (OR 2.09, 95% CI 1.44, 3.03, P < 0.001). It also elevated diagnostic yield of malignant PPLs (OR 1.67, 95% CI 1.26, 2.22, P < 0.001) and PPLs in the bilateral upper lobes (OR 1.50, 95% CI 1.09, 2.08, P = 0.014). Conclusions: Navigation bronchoscopy enhanced diagnostic yield when compared to non-navigation bronchoscopy, particularly for PPLs in the peripheral third lung, PPLs being bronchus sign positive, PPLs ≤ 20 mm, malignant PPLs and PPLs in the bilateral upper lobes. Key pointsThe current study provided systematic evaluation on the diagnostic value of navigation bronchoscopy by comparing it with non-navigation bronchoscopy, and exploring the factors affecting the diagnostic yield.

Background: It is very difficult to obtain samples of peripheral pulmonary ground-glass opacity lesions (GGOs) by traditional transbronchial biopsy. This study was conducted to evaluate the diagnostic efficacy and safety of transbronchial cryobiopsy (TBCB) of GGOs using a newly developed ultrathin cryoprobe with an outer diameter of 1.1 mm. Methods:We retrospectively analyzed 20 patients with 23 GGOs who underwent TBCB using the ultrathin cryoprobe from October 2018 to November 2019 in the Shanghai Chest Hospital. The TBCB procedure was performed under the guidance of virtual bronchoscopic navigation (VBN), electromagnetic navigation bronchoscopy (ENB), endobronchial ultrasound, and fluoroscopy. We collected the baseline information of participants, reported diagnostic yield and complications, and analyzed factors may have affected the diagnostic yield.Results: A total of 23 GGOs (12 pure GGOs, 11 mixed GGOs), with an average diameter of 21.58± 11.88 mm, underwent TBCB, and the diagnostic yield was 82.61% (19/23). Of the 19 GGOs diagnosed by TBCB, 12 were adenocarcinomas, 5 were inflammation, 1 was occupational interstitial lung disease, and 1 was a pulmonary meningothelial-like nodule. The remaining 4 undiagnosed lesions were confirmed to be adenocarcinomas by further analysis. The diagnostic yield was unchanged by factors including size (GGOs ≥20 mm, GGOs <20 mm), navigation (VBN, ENB), fluoroscopic visibility (visible, invisible), GGOcomponent (pure GGOs, mixed GGOs), and guide sheath (K-201, K203). There was no presentation of pneumothorax or severe hemorrhage. Conclusions:The ultrathin cryoprobe is feasible, safe, and has a high diagnostic yield in the diagnosis of pulmonary GGOs. There is vast potential for the ultrathin cryoprobe as a tool for the diagnosis of GGOs, especially for cases suspicious of early-stage lung cancer.

BackgroundAlthough numerous efforts have been made, the pathogenesis underlying lung squamous-cell carcinoma (SCC) remains unclear. This study aimed to identify the CNV-driven genes by an integrated analysis of both the gene differential expression and copy number variation (CNV).ResultsA higher burden of the CNVs was found in 10–50 kb length. The 16 CNV-driven genes mainly located in chr 1 and chr 3 were enriched in immune response [e.g. complement factor H (CFH) and Fc fragment of IgG, low affinity IIIa, receptor (FCGR3A)], starch and sucrose metabolism [e.g. amylase alpha 2A (AMY2A)]. Furthermore, 38 TFs were screened for the 9 CNV-driven genes and then the regulatory network was constructed, in which the GATA-binding factor 1, 2, and 3 (GATA1, GATA2, GATA3) jointly regulated the expression of TP63.ConclusionsThe above CNV-driven genes might be potential contributors to the development of lung SCC.