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To our knowledge, this is the first comprehensive study investigating major oncogenic driver mutations in a large cohort of AdSqLC patients in a Chinese population. The findings suggest that it will be clinically valuable to investigate the growth pattern of glandular component in AdSqLCs.

Long non‐coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of non–small cell lung cancer (NSCLC). However, how lncRNA deleted in lymphocytic leukaemia 2 (DLEU2) contributes to NSCLC remains undocumented. The clinical significance of lncRNA DLEU2 and miR‐30a‐5p expression in NSCLC was analysed by using fluorescence in situ hybridization and TCGA cohorts. Gain‐ and loss‐of‐function experiments as well as a NSCLC tumour model were executed to determine the role of lncRNA DLEU2 in NSCLC. DLEU2‐sponged miR‐30a‐5p was verified by luciferase reporter, and RIP assays. Herein, the expression of lncRNA DLEU2 was elevated in NSCLC tissues, and its high expression or low expression of miR‐30a‐5p acted as an independent prognostic factor of poor survival and tumour recurrence in NSCLC. Silencing of lncRNA DLEU2 repressed the tumorigenesis and invasive potential of NSCLC, whereas re‐expression of lncRNA DLEU2 showed the opposite effects. Furthermore, lncRNA DLEU2 harboured a negative correlation with miR‐30a‐5p expression in NSCLC tissues and acted as a sponge of miR‐30a‐5p, which reversed the tumour‐promoting effects of lncRNA DLEU2 by targeting putative homeodomain transcription factor 2 in NSCLC. Altogether, lncRNA DLEU2 promoted the tumorigenesis and invasion of NSCLC by sponging miR‐30a‐5p.

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BackgroundThe predictive and prognostic impact of factors associated with visceral pleural invasion (VPI) on survival and recurrence in patients with resected lung adenocarcinomas is not clearly defined.Patients and methodsA total of 505 consecutive patients with stage Ia–IIIa lung adenocarcinomas treated with radical resection were included. The predominant growth pattern was classified according to the new classification system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. The correlations of VPI with clinical and pathologic parameters were analyzed.ResultsThe incidence of VPI was significantly lower in lepidic predominant group (15.5% vs 4.5%, P<0.001) and higher in solid and micropapillary predominant group (28.6% vs 17.6%, P=0.004 and 14.7% vs 4.2%, P<0.001, respectively). VPI correlated with higher risk in regional postoperative recurrence (hazard ratio, 2.341; 95% confidence interval, 1.564–3.504) and distant recurrence (hazard ratio, 2.193; 95% confidence interval, 1.665–2.89) in surgically resected lung adenocarcinomas. However, when growth patterns of adenocarcinoma were lumped into multivariate analysis, VPI was not a significant independent predictive factor for survival (P=0.854 for overall survival [OS] and P=0.575 for disease-free survival [DFS]) and recurrence (P=0.38 for regional recurrence and P=0.089 for distant recurrence). Of the 95 patients with stage Ib, those who received adjuvant chemotherapy had longer DFS and OS than the patients who received no chemotherapy after surgery. However, these differences in DFS and OS did not reach statistical significance (P=0.063 for DFS, P=0.85 for OS).ConclusionVPI was associated with solid and micropapillary histology. In addition, stage Ib patients with solid histologic subtype tumor showed longer DFS and OS, highlighting a potential benefit in this subgroup of patients and necessitating the need for larger clinical trials.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significant benefits to patients with non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations; however, acquired resistance limits their long-term efficacy. Therefore, it remains an urgent requirement to discover the underlying mechanisms and investigate novel therapeutic strategies for overcoming the resistance to EGFR TKIs. The present study aimed to determine the mechanism underlying the resistance of NSCLC cells to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, the osimertinib-resistant NSCLC cell sub-line HCC827/OR was established in the present study. It was found that the expression levels of Bcl-2 and Bcl-xL were significantly upregulated in resistant cells compared with sensitive cells. Furthermore, the suppression of Bcl-2 and Bcl-xL through small interfering RNA-mediated gene knockdown or using a small molecule specific inhibitor ABT-263 re-sensitized HCC827/OR cells to osimertinib treatment. Moreover, the combined treatment of HCC827/OR cells with ABT-263 and osimertinib enhanced the rate of cell apoptosis through the mitochondrial apoptotic pathway. Finally, ABT-263 was able to overcome the resistance of osimertinib in xenograft tumor models. In conclusion, these findings may provide an improved concept for the development of a novel combined therapeutic strategy for the treatment of NSCLC resistance to EGFR TKIs.

BackgroundStage III Non-small cell lung cancer (NSCLC) is a heterogenous disease with novel treatment options. Recently, immunotherapy has attracted a lot of attention for advanced NSCLC.ObjectiveThe objective of our study was to assess the efficacy and safety of neoadjuvant immuno-chemotherapy for resectable stage III NSCLC.MethodsWe analyzed 11 stage III primary NSCLC surgical cases who had undergone standard lobectomy or bronchial sleeve resection and lymph node dissection between December 2020 and July 2021. The data analyzed included basic clinical features, serum levels of key biomarkers, clinical efficacy in the perioperative period, postoperative pathological results, postoperative complications and the incidence rates of Immune-Related Adverse Events.ResultsEleven patients were enrolled in our study with a mean age of 67.7 ± 4.8 years, and 10 patients being men with former or current smoking history. Squamous carcinoma (10/11, 91.1%) was the most common cancer type. Six patients had stage IIIa, five had stage IIIb. All patients received two or three cycles of neoadjuvant immuno-chemotherapy, with the median duration between the last treatment and surgery being 39 days (range, 32–46 days). All patients underwent R0 resection with ten patients undergoing single-port video-assisted thoracoscopic surgery. The median operative time was 170 min (range, 120–240 min). Only three (3/11, 27.3%) patients experienced mild postoperative complications and the mean hospital stay time was 6.9 days (range, 4–15 days). Nine (9/11, 81.8%) patients experienced major pathological response of which seven (7/11, 63.6%) was complete pathological response in postoperative results. The pathological stage was downgraded in 10 (10/11, 91.1%) patients, and although the incidence of Immune-Related Adverse Events was slightly higher (8/11, 72.7%), most events were grade 1–2 and did not delay surgery.ConclusionOur study demonstrated that neoadjuvant immuno-chemotherapy is feasible and relatively safe for resectable stage III primary NSCLC patients. We hope this new neoadjuvant immuno-chemotherapy model can improve overall survival and open a new era for stage III primary NSCLC patients.