To clarify whether arsenic could exert inhibitory effects on tumor cells in pleural effusions of patients with non-small cell lung cancer (NSCLC), 36 NSCLC pleural effusion samples were collected from Changzheng Hospital and Ruijin Hospital, from 2019 to 2022. The genotype of epidermal growth factor receptor (EGFR) was identified. Tumor cells were isolated and treated with arsenic trioxide (ATO) or/and gefitinib. Additionally, six patients were intrapleurally administrated with ATO. Results showed that 25 samples bore EGFR wild type (WT) and 11 harbored EGFR mutations, including 6 with L858R, 3 with ΔE746-A750, and 2 with T790M. ATO diminished the number of tumor cells from patients with WT and mutant EGFR, down-regulated the expression or phosphorylation of EGFR, pmTOR, PI3K, PTEN, and p4E-BP1, and up-regulated the expression of LC3. Immunofluorescent experiments showed that ATO enhanced LC3 and P62. By contrast, gefitinib was only effective in those harboring EGFR sensitizing mutations. Notably, in patients with intrapleural ATO injection, the pleural effusion underwent a bloody to pale yellow color change, the volume of the pleural effusion was reduced, and the number of the tumor cells was significantly reduced. In conclusion, arsenic is effective against NSCLC with various EGFR genotypes in vitro and in vivo, and potentially circumvents gefitinib resistance.

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer and remains a leading cause of cancer-related mortality worldwide. Althou

Background Lung adenocarcinoma (LUAD) is one of the most prevalent and lethal malignancies worldwide. Synaptotagmins (SYTs) are a group of transmembrane proteins of which dysregulation has been reported in various cancers. Here, we analyzed the role of SYT2/11/13/15 in LUAD using bioinformatic methods.Methods In TCGA-LUAD cohort, we compared the expression level of SYTs in LUAD and normal tissue. To determine their biological functions, protein-protein interaction (PPI) network was constructed and GO/KEGG analysis were performed. GSEA were used to find the pathway changes. DNA methylation changes in SYT2/11/13/15 were investigated based on MethSurv. The impact on immune cell infiltration were revealed using TIMER database. The diagnostic power of SYT2/11/13/15 were studied using Kaplan-Meier plotter, diagnostic receiver operating characteristic (ROC) curves, nomogram model, and Cox regression analysis.Results In brief, we found that SYT2/13 were upregulated and SYT11/15 were down-regulated in LUAD, high expression of SYT2/11/15 predicted a favorable prognosis while SYT13 indicated a poor one. Functional analysis showed that SYTs mainly involved in neuroactive signal transduction. Several CpG islands of SYTs genes correlated to poor prognosis were identified. Cox regression analysis showed that SYT2/11/13/15 are independent risk factors for overall survival (OS) and disease-specific survival (DSS) of LUAD patients. SYT11/15 were closely related to immune infiltration in LUAD, SYT11 correlated to CD8 + T cell, dendrite cell (DC), macrophages. SYT15 correlated to CD4 + T cell, DC, and myoid derived suppressor cell (MDSC).Conclusion To sum up, we found that SYT2/11/13/15 were differentially expressed and were potential prognostic biomarkers, and may modulate immune infiltration in LUAD.

Background: Circulating tumor cells (CTCs), programmed cell death-ligand 1 (PD-L1) positive CTCs (PD-L1⁺CTCs) and extracellular vesicles (EVs) are important biomarkers for predicting treatment efficacy. This study comprehensively investigated the factors used to forecast chemoimmunotherapy efficacy in advanced lung cancer. Methods: The CellSearch system, EVAnalyzer plugin and single-cell whole-exome sequencing (WES) were used to analyze these factors. Results: It was found that CTCs were highly detectable in advanced lung cancer. The median number of baseline CTCs was significantly lower in non-small cell lung cancer (NSCLC) than small cell lung cancer (SCLC) (3 vs. 38, p < 0.0001), as were PD-L1⁺CTCs (1 vs. 5, p = 0.0014). PD-L1⁺CTCs decreasing after two treatment circles was associated with superior ORR. Baseline median EV counts were elevated in NSCLC compared with SCLC (11,700 vs 1371, p = 0.017). Patients exhibiting divergent dynamic trends between EVs and CTC/PD-L1⁺CTCs demonstrated better treatment response. The combination of CTCs, PD-L1⁺CTCs and EVs improved predictive efficacy for both NSCLC and SCLC. CTC sequencing identified multiple pathogenic somatic variants, which might affect immunotherapy efficacy. Conclusions: Serial dynamic monitoring of CTCs, PD-L1⁺CTCs and EVs, as well as CTC sequencing, enables the early prediction of chemoimmunotherapy response and the discovery of mechanisms that affect immunotherapy efficacy in advanced lung cancer.