BackgroundFBXW7 m6A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear.MethodsThe correlation between FBXW7 and various genes related to m6A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m6A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m6A modification on LUAD development.ResultsDecreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m6A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m6A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m6A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored the suppression of LUAD cells in vitro and in vivo.ConclusionsOur findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development.

Objective. To evaluate the prognostic value of the immune checkpoint inhibitor prognostic index (ICPI), based on the albumin (ALB) and derived neutrophil-to-lymphocyte ratio (dNLR), for nonsmall cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). Methods. We conducted a multicentre retrospective study with an ICIs cohort (n = 143) and a chemotherapy control cohort (n = 84). A Cox proportional hazards regression and logistic regression model were used to find the independent risk factor for progression-free survival (PFS) and overall survival (OS) and disease control rate (DCR) in NSCLC patients. The Kaplan–Meier was used to evaluating the PFS and OS. Results. The ALB <35 g/L and dNLR >3 were correlated with worse PFS and OS for NSCLC patients receiving ICIs, respectively. The moderately high-risk ICPI had a significantly increased risk of progression (hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.14–2.91; P = 0.012 ) and of death (HR 2.33, 95% CI 1.12–4.87; P = 0.024 ) and of nondisease control (odds ratio (OR) 3.05, 95% CI 1.19–7.83; P = 0.021 ) and was correlated with worse PFS and 1-year survival rates (4.0 months vs. 7.2 months; P = 0.001 ; 44.3% vs. 76.1%; P = 0.001 ) compared with low-risk ICPI when it was characterized two groups. When ICPI was further divided into three groups, the results showed that the high-risk ICPI was correlated with worse PFS and 1-year survival rates. However, there was no difference in the chemotherapy cohort. Conclusion. The ICPI was correlated with worse outcomes for NSCLC patients receiving ICIs but not for patients with chemotherapy.

Background More and more peripheral pulmonary lesions (PPL) have been found following the increased utilization of chest CT in China. But how to identify the nature of PPL accurately, safely and economically is the concern of Chinese doctors. The combination of radial endobronchial ultrasonography with a guide sheath and virtual bronchoscopic navigation was a deluxe scheme to indicate the pathology of peripheral pulmonary lesions in nation’s current medical level. This study aimed to compare the diagnostic yield, safety and health economics of EBUS-GS-VBN versus radial ultrasonic small probe plus thin bronchoscopy (EBUS) for diagnosis of PPLs. Methods This study was a single-institution retrospective review of PLLs examined by using EBUS-GS-VBN or radial EBUS between March 2018 and September 2018 consecutive. The diagnostic yields, accuracy, operation time, complications, factors influencing the diagnostic outcome, tissue genetic test rate and medical cost were analyzed separately. Results there was no significant difference in the diagnostic yield between the two groups (92.31% vs 88.57%, p = 0.594). Although the searching time of EBUS-GS-VBN was shorter (1.47 ± 0.49 min vs 2.12 ± 1.36 min, p < 0.001), procedure time was extended (24.07 ± 5.53 min vs 17.41 ± 4.38 min, p < 0.001). The diagnosis yield of malignancy and benign disease were equal (84.62% vs 100% and 95.35% vs 84%). There was no difference in the rate of gene testing between the two groups (75% vs 70.58%), while the incidence of Intrapulmonary hemorrhage in the EBUS-GS-VBN group was significantly descended. Moreover, the average expense of EBUS-GS-VBN was higher than that of EBUS-GS (6315 ± 1817 RMB vs 3128 ± 1086RMB). Conclusion When performing TBLB of PLLs, we found EBUS-GS-VBN to be similar to EBUS in accuracy. Although the founding lesion time of EBUS-GS-VBN group were significantly shorter, the total examination time was longer. Furthermore, the complications of EBUS-GS-VBN group were fewer. There was no difference in genetic testing between the two groups. It is worth noting that the cost and radiation exposure was lower of EBUS group patients. Trial registration: retrospectively registered