USP5 influences immune infiltration and prognosis in non-small-cell lung cancer
Yonghong Xu1, Yifei Xie2, Jian Zhao2
1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, PR China; Department of Respiratory and Critical Care Medicine, The second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Suzhou Key Laboratory for Respiratory Diseases, Suzhou, Jiangsu 215006, PR China; Institute of Respiratory Diseases, Soochow University, Suzhou, Jiangsu 215006, PR China.
Background:
USP5, a deubiquitinating enzyme, is linked to various cancers. However, its relationship with immune infiltration and its prognostic significance in non-small-cell lung cancer (NSCLC) remains to be determined.
Methods:
USP5 expression patterns in NSCLC were analyzed using data sourced from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Functional enrichment analyses were performed to predict the role of USP5 in NSCLC development, and Hub genes were identified through a protein-protein interaction (PPI) network. Immune cell infiltration was assessed via single-sample gene set enrichment analysis, while the prognostic significance of USP5 was evaluated using the Kaplan-Meier method and Cox regression analysis. To facilitate survival rate predictions at different time points, a prognostic model was developed. Previous findings were validated using real-time PCR and in vitro functional assays in NSCLC cell lines.
Results:
USP5 expression was found to be markedly elevated in NSCLC tissues when compared to normal tissues. Functional enrichment analysis revealed the involvement of USP5 in regulating key pathways linked to lung adenocarcinoma development. PPI network analysis revealed several potential interactions contributing to NSCLC progression. A correlation was observed between higher USP5 levels and the reduced presence of immune cells (e.g., macrophages, CD8 +T cells, NK cells, and iDCs) within the tumor microenvironment. ROC curves confirmed the prognostic value of USP5 for NSCLC. Functional studies in NSCLC cell lines confirmed the molecular effects of USP5 on NSCLC development.
Conclusions:
USP5 appears to be a reliable marker for diagnosing NSCLC and predicting its prognosis. Further investigation into the role of USP5 in immune responses may aid in the development of immunotherapies for NSCLC.
