Transcriptomic profiling of a lung cancer animal model induced by emotional stress

Because the transcriptional changes linking emotional stress to lung cancer progression are still unclear, we established a mouse model of lung adenocarcinoma in which chronic stress was applied before and after inoculation with A549 human lung cancer cells. In this study, four-week-old BALB/c nude mice were randomly assigned to an emotional-stress group or a control group. Emotional-stress mice were subjected to a validated chronic stress paradigm combining restraint, food or water deprivation, etc. At sacrifice, serum levels of inflammatory factors, including IL-s, cortisol, etc., were quantified by ELISA and tumor tissues were analyzed immunohistochemically for P53, CD4, EGFR and Ki-67, etc. Whole-transcriptome RNA-sequencing was performed, and differentially expressed genes were identified. Functional enrichment was carried out using KEGG and GO analyses. Tumors in Emotional-stress mice grew significantly faster, reaching 137.7 ± 22.78 mm³ versus 39.66 ± 11.00 mm³ in control mice on day 30 ( P < 0.001). Despite this difference in tumor growth, serum cytokine levels and the staining intensities of EGFR and Ki-67 were not significantly different between groups. Heatmap-based screening identified 27 candidate genes (16 up-regulated and 11 down-regulated in Emotional-stress tumors) showing consistent expression trends across pairwise comparisons. Subsequent DESeq2 analysis confirmed that 21 of these genes reached statistical significance (p-adj < 0.05). Bioinformatic analyses indicated that these genes were enriched in pathways related to primary immunodeficiency, ATP-binding cassette transporters, base excision repair, etc. qPCR validation of three representative DEGs (PARP2, TBC1D3D, DCAF11) confirmed the RNA-seq expression trends. Overall, this study provides a transcriptomic resource for an emotion-stress-driven lung cancer model and offers a starting point for future work on the molecular links between chronic stress and lung tumor progression.