Purposes: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) used for patients with gefitinib (first-generation EGFR-TKI) resistance, but osimertinib resistance inevitably occurs. Therefore, it is necessary to explore the mechanisms of osimertinib resistance. Materials and Methods: We performed quantitative real-time polymerase chain reaction to detect hsa_circ_0007312 (circ7312), miR-764, and MAPK1 expressions in tissues and cells. Western blotting was used to detect protein levels in cells. Cell Counting Kit-8, apoptotic, and Transwell assays were used to explore biological functions. Luciferase assays were used to identify the interactions between circ7312 and miR-764, MAPK1 and miR-764. A xenograft experiment was performed to clarify the role of circ7312 in vivo. Public datasets were used to identify the relation between circ7312 expression and the cell half maximal inhibitory concentration value of osimertinib in 41 lung adenocarcinoma cell lines. The Student t-test, Kaplan-Meier analysis, and Pearson correlation analysis were used in data analysis. Results: We found that circ7312 knockdown increased miR-764 expression and decreased MAPK1 expression, and circ7312 regulated MAPK1 by sponging miR-764. In addition, high circ7312 expression has significant positive correlation with osimertinib IC50 values, circ7312 knockdown decreased the cell half maximal inhibitory concentration value of osimertinib and increased pyroptosis and apoptosis by sponging the miR-764/MAPK1 axis. We also found that circ7312 and MAPK1 were highly expressed in tumor tissues and related to poor prognosis. Xenograft experiments revealed that circ7312 knockdown decreased osimertinib resistance in vivo. Conclusion:We demonstrated that the inhibition of circ7312 decreased osimertinib resistance by promoting pyroptosis and apoptosis via the miR-764/MAPK1 axis, providing a novel target for osimertinib resistance therapy.
The aim of the study was to investigate the preoperative factors affecting the survival of patients with resectable peripheral nonsmall cell lung cancer (NSCLC) to improve the management of NSCLC.Methods: One hundred ninety-nine patients with peripheral NSCLC diagnosed clinically without lymph node metastasis were enrolled. The preoperative computed tomography characteristics of the tumors were retrospectively analyzed and the preoperative clinical data were collected. The size of the solid components for lung adenocarcinomas containing ground-glass opacity (GGO) component were measured. Kaplan-Meier method with log-rank test was used to compare overall survival (OS) between groups. Univariate and multivariate cox regression analyses were used to identify prognostic factors.Results: Survival analysis showed that the OS of the group with a tumor of 3 cm or less was longer than that of the group with a tumor greater than 3 cm, the OS of the group with GGO component was superior to that of the group without GGO component, and the OS of the group with elevated carcinoembryonic antigen (CEA) levels was inferior to that of the group with normal CEA levels. Multivariate Cox regression analysis showed that tumor size, density, and preoperative CEA level were independent factors affecting OS, with hazard ratios of 2.401, 0.457, and 1.948, respectively. The analysis of lung adenocarcinomas with GGO component demonstrated that the mean size of the solid component in the nonsurviving group was significantly larger than that in the surviving group (mean, 23 ± 6.4 vs 8.6 ± 7.0 mm). The area under the receiver operating characteristic curve of the solid component size of lung cancer containing GGO component to predict postoperative death was 0.932. Conclusions:Tumor size, density, and preoperative CEA level were independent prognostic factors of patients with resectable peripheral NSCLCs. Preoperative computed tomography findings can be valuable for predicting the prognosis of patients with NSCLC after surgery.
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