ScholarWorks@중앙대학교

초록

BACKGROUND: The mechanical remodeling of tumor microenvironment is critical for non-small cell lung cancer (NSCLC) progression. Dual-specificity phosphatase 23 (DUSP23) has been previously identified as a mechano-responsive gene, but its role in NSCLC progression remains unknown. OBJECTIVE: We aim to elucidate the clinical significance of DUSP23 in NSCLC progression. METHODS: We analyzed the expression of DUSP23 in cancer using polyacrylamide hydrogels designed to mimic the stiffness of normal (soft; ~0.5 kPa) and cancerous (stiff; ~40 kPa) tissues. The prognostic significance of DUSP23 expression in patients was examined using public databases. Additionally, we conducted various cell-based assays and transcriptomic analyses in DUSP23-silenced NSCLC cell lines. A risk score prognosis model was constructed using univariate Cox regression and Kaplan-Meier analysis. RESULTS: Our findings show that DUSP23 is upregulated in stiff matrices and is highly associated with poor prognosis in patients with solid cancers such as NSCLC and breast cancer. Silencing of DUSP23 resulted in decreased cell proliferation and invasion. Transcriptomic profiling revealed that 182 genes were downregulated, and 230 genes upregulated following DUSP23-depletion. Notably, 182 downregulated genes were enriched in cancer-related pathways, including cell cycle progression and cytoskeleton organization. Through KEGG pathway analysis, we identified 11 cancer-related genes and developed a prognostic risk model. In this model, the high-risk group of NSCLC patients exhibited significantly shorter overall survival compared to low-risk group, based on public datasets. CONCLUSIONS: Our study demonstrates the clinical significance of DUSP23 as a prognostic marker in NSCLC and highlights its potential role of DUSP23 in promoting NSCLC progression. © 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.

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