Identification of PSMD11 as a novel cuproptosis‐ and immune‐related prognostic biomarker promoting lung adenocarcinoma progression

Abstract

Abstract Background Due to the unfavorable prognosis associated with lung adenocarcinoma (LUAD), the development of targeted therapies and immunotherapies is essential. Cuproptosis, an emerging form of regulated cell death, is implicated in mitochondrial metabolism and is induced by copper ions. This study aimed to explore the prognostic value of cuproptosis‐ and immune‐related genes (CIRGs) in LUAD. Methods We used The Cancer Genome Atlas database to develop a prognostic prediction model for LUAD patients based on eight CIRGs. Using Cox regression analysis, we determined that the CIRG signature is a reliable, independent prognostic factor. We further identified PSMD11 as a critical CIRG and performed immunohistochemistry to study the protein expression levels of PSMD11 in LUAD tissues. We also investigated the impact of PSMD11 on the biological behavior of lung cancer cell lines. Results We found that patients with low PSMD11 expression levels displayed an improved prognosis compared with those with high PSMD11 expression levels. Overexpression of PSMD11 enhanced proliferation, migration, invasion, and tumor growth of lung carcinoma cell line A549, while PSMD11 knockdown diminished proliferation, migration, invasion, and tumor growth of lung carcinoma cell line PC9. Additionally, we discovered that PSMD11 expression was positively correlated with the infiltration of myeloid‐derived suppressor cells and the increased expression of immunosuppressive molecules. Conclusion These findings suggest that PSMD11 may serve as a valuable prognostic biomarker and therapeutic target for LUAD.

Keywords

• cuproptosis
• immune cells
• lung adenocarcinoma
• prognosis
• PSMD11