Non-small cell lung cancer (NSCLC) is the most common form of cancer, resulting in cancer-related deaths worldwide. Exosomes, a subclass of extracellular vesicles, are produced and secreted from various types of cells, including cancer cells. Cancer-derived exosomes can deliver nucleic acids, proteins, and lipids to provide a favorable microenvironment that supports tumor growth through enhancing cell proliferation and metastasis. Our results showed that miR-224-5p was upregulated in NSCLC patient tissues and cell lines, with a tumor-promoting phenotype. Meanwhile, exosome-derived miR-224-5p induced cell proliferation and metastasis in NSCLC and human lung cells. Moreover, we characterized the androgen receptor (AR) as a direct target of miR-224-5p. Tumor xenograft assay experiments revealed that overexpression of miR-224-5p drove NSCLC tumor growth via the suppression of AR and the mediation of epithelial-mesenchymal transition (EMT). Collectively, our results suggest that miR-224-5p-enriched exosomes promote tumorigenesis by directly targeting AR in NSCLC, which may provide novel potential therapeutic and preventive targets for NSCLC.

Background: We aim to establish neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) related nomograms based on the clinical data and peripheral blood markers to predict the survivals of patients with limited-stage small-cell lung cancer (LS-SCLC). Methods: A total of 299 LS-SCLC patients after surgery were enrolled in this study. Univariate and multivariate analyses were conducted to select independent prognostic factors to develop the nomograms and then subjected to bootstrap internal validation. The optimal cutoff value of NLR and PLR before surgery was calculated by X-tile (version 3.6.1) and the overall survival (OS) was analyzed by Kaplan-Meier method and compared by log-rank test. Results: According to the X-tile calculation, the NLR value and PLR cutoff values are 2.6 and 156.7, respectively. The prognosis of patients with elevated NLR or PLR value was significantly worse than patients with lower NLR (HR =1.798, 95% CI: 1.284–2.518, P=0.001) or PLR (HR =1.781, 95% CI: 1.318–2.407, P<0.001) value. Two Nomograms were developed according to the two multivariate cox regression models based on NLR and PLR. Concordance index (C-index) curves and calibration curves show that the two models have a better effect in predicting prognosis. At the same time, compared with the tumor node metastasis (TNM) staging system, our models also show better accuracy and stability. Conclusions: Elevated NLR and PLR predict poor prognosis in their respective nomograms in patients with LS-SCLC.