Background
The 26S non-ATPase regulatory subunit 11 (PSMD11) is a multiprotein complex that participates in the ATP-dependent degradation of ubiquitinated proteins and is essential to the regulation of embryonic stem cell proteasome activity. PSMD11 has been demonstrated to be a factor contributing to the emergence and progression of cancer cells. However, the prognostic value and potential biological function of PMSD11 in lung adenocarcinoma (LUAD) remains unclear. The
Conclusions
These results indicate that PSMD11 has the potential to be a novel therapeutic target and sensitive biomarker for patients with LUAD.
Methods
We primarily endeavored to comprehensively investigate the prognostic and predictive value of PSMD11 in patients with LUAD. Additionally, we aimed to further clarify the underlying mechanisms of PSMD11 in LUAD tumorigenesis and progression via rigorous bioinformatics analyses, including expression analysis, survival analysis, clinicopathological analysis, immune microenvironment analysis, somatic mutation analysis, drug analysis, and cuproptosis analysis. Subsequently, we examined effect of PSMD11 expression on immune escape in a non-small cell lung cancer (NSCLC) cell-T cell coculture model.
Results
We found that PSMD11 had a significantly higher expression in LUAD tissues than in normal lung tissues. Three clinical characteristics (age, stage, and overall survival event) exhibited significant differences between the PSMD11 high- and low-expression groups. In biological function, PSMD11 appears to exert its tumorigenic effects predominantly in pathways related to DNA replication and membrane-gated channel functions. Notably, we observed that PSMD11 exhibited the strongest positive correlation with T helper 2 cells, gamma-delta T cells, and T regulatory cells and the highest negative correlation with B cells, mast cells, and CD8+ T cells. Furthermore, we found that the expression of cuproptosis genes (DLAT, DLD, and PDHA1) was positively correlated with the expression of PSMD11 (P<0.001). Conclusions: These results indicate that PSMD11 has the potential to be a novel therapeutic target and sensitive biomarker for patients with LUAD.