Advanced lung cancer is considered to exhibit a poor prognosis; however, the pulmonary lymphoepithelioma‑like carcinoma (LELC), a rare subtype of non‑small cell lung cancer (NSCLC), exhibits an improved prognosis, compared with non‑LELC. The present study aimed at investigating the clinical manifestation, imaging characteristics, pathology, tumor markers, treatment and prognosis of primary LELC of the lung. A total of 14 patients with pulmonary LELC were confirmed by surgery and pathology. Clinical data of those patients were retrospectively reviewed including age, sex, smoking history, symptoms, computed tomography (CT) results, Epstein‑Barr virus‑encoded RNA (EBER) status, treatment and outcomes. In the present study, there were 7 males and 7 females who ranged in age between 22 and 64 years (mean, 51.21±11.37 years) and who all were from eastern China. The tumor‑node‑metastasis stage ranged between stages I and IV, with 71.43% of the patients at advanced stage (stages III and IV). The results of the present study identified 100% positive expression of EBER. Tumors located centrally were of significantly increased size, compared with peripheral tumors (P<0.05), and lymphadenopathy was more common in patients with advanced stage (P<0.05). The majority of patients were treated with surgery, platinum‑based chemotherapy or radiotherapy. At time of writing, 12 patients were alive and the longest survival time was 60 months. Pulmonary LELC typically affected young patients and was not associated with smoking history; however, pulmonary LELC was associated with Epstein‑Barr virus infection in the Asian population. The majority of patients were in early or locally advanced stages and exhibit an improved prognosis compared with other types of NSCLC. Pulmonary LELC was sensitive to chemotherapy and surgery, with postoperative chemotherapy‑based multimodality treatment recommended.

Lung cancer is considered to be one of the world's deadliest diseases, with non‑small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. The present study aimed to investigate the role and underlying mechanisms of interleukin‑21 (IL‑21), and its receptor IL‑21R, in NSCLC. Lung tissues and blood samples of NSCLC were used to measure IL‑21, IL‑21R and programmed death 1 ligand 1 (PD‑L1) expression using ELISA, western blot and immunohistochemistry analyses. Following treatment with different doses of IL‑21, the proliferation, invasion and migration of human NSCLC cell line A549 was evaluated using a cell counting kit‑8, colony formation, Transwell and scratch wound healing assays, respectively. Additionally, IL‑21R and PD‑L1 expression in A549 cells was detected using western blot analysis and immunofluorescence. IL‑21R silencing was subsequently used to investigate its effects in cell proliferation, invasion and migration. PD‑L1, IL‑1β and tumor necrosis factor α (TNF‑α) expression were measured. Finally, Wnt/β‑catenin signaling expression was evaluated using western blot analysis following treatment with IL‑21. Cells were then treated with lithium chloride (LiCl), which is an agonist of Wnt/β‑catenin signaling, and the levels of PD‑L1, IL‑1β and TNF‑α were detected. The results revealed that IL‑21 and IL‑21R expression in the lung tissues and blood samples of patients with NSCLC were decreased, while PD‑L1 expression was increased, compared with normal tissues or healthy controls. Treatment of A549 cells with IL‑21 upregulated IL‑21R expression, downregulated PD‑L1 and inhibited cell growth and metastasis in a dose‑dependent manner. Following IL‑21R silencing, the effects of IL‑21 treatment were reversed, suggesting that IL‑21 acted on A549 cells through binding to IL‑21R. In addition, the results demonstrated that IL‑21 treatment reduced the expression levels of proteins associated with the Wnt/β‑catenin signaling, whereas activation of Wnt/β‑catenin signaling with the LiCl agonist upregulated PD‑L1, IL‑1β and TNF‑α expression. In conclusion, the IL‑21/IL‑21R axis reduced the growth and invasion of NSCLC cells via inhibiting Wnt/β‑catenin signaling and PD‑L1 expression. The present results may provide a novel molecular target for NSCLC diagnosis and therapy.

Background: Pulmonary fibrosis arises from various etiologies, often associated with elevated levels of reactive oxygen species (ROS) stress and activation of pro-fibrotic signaling pathways. The chemotherapeutic drug bleomycin has been shown to exacerbate pulmonary fibrosis during anti-tumor treatment. Further research is needed to combat bleomycin-induced fibrosis.Aim: This investigation aims to identify critical mediators of bleomycin-induced pulmonary fibrosis and evaluate the therapeutic potential of mitochondria-targeted ubiquinone (MitoQ) in attenuating fibrotic pathogenesis.Methods: A bleomycin-induced pulmonary injury mouse model and fibroblast cell culture were established, followed by histopathology evaluation, molecule interaction analysis, cytokine quantification, intervention assay, and flow cytometry.Results: We analyzed RNA-seq data from a bleomycin-induced pulmonary fibrosis mouse model and identified a network of oxidative stress-related fibrosis genes centered on Tgfb1. In fibroblast cell lines, bleomycin exposure elevated mitochondrial and cellular ROS, increased mitochondrial mass and the MDR^low/MTG^high cell ratio, downregulated genes linked to ROS scavenging and mitochondrial function, and upregulated transcription of pro-fibrotic molecules. MitoQ effectively reduced mitochondrial ROS, alleviated mitochondrial swelling, and restored transcription of genes involved in mitochondrial redox balance and function. Compared to conventional ubiquinone, MitoQ exhibited significantly greater antifibrotic efficacy, effectively attenuating bleomycin- and TGF-β1-induced fibroblast activation in vitro. In bleomycin-treated mice, MitoQ treatment with markedly suppressed pro-fibrotic molecule transcription and inhibited pulmonary fibrosis progression.Conclusion: These findings not only advance our understanding of the interplay between oxidative stress and pro-fibrotic signaling in bleomycin-induced pulmonary fibrosis but also provide experimental data supporting the use of mitochondria-targeted antioxidant in the treatment of this condition.