Validation of a Novel Cuproptosis-Related Prognostic Gene Marker and Differential Expression Associated with Lung Adenocarcinoma.

Background: Cuproptosis induction is seen as a promising alternative for immunotherapies and targeted therapies in breast cancer. The objective of this research was to examine the prognostic and biological importance of cuproptosis-related genes (CRGs) in lung adenocarcinoma (LUAD).

Methods: The following methods were used: GSE10072 dataset and TCGA database analysis, differential expression analysis of CRGs, and biological function (BP) and signaling pathway enrichment analysis, prognostic analysis and clinical analysis of CRGs, construction of the prognostic signature and RNA modified genes and miRNA analysis of CRGs in LUAD, immunoinfiltration analysis and immunohistochemical staining of DβH, UBE2D3, SOD1, UBE2D1 and LOXL2.

Results: AOC1, ATOX1, CCL8, CCS, COX11, CP, LOXL2, MAP2K2, PDK1, SCO2, SOD1, UBE2D1, UBE2D3 and VEGFA showed significantly higher expression, while ATP7B, DβH, PDE3B, SLC31A2, UBE2D2, UBE2D4 and ULK2 showed lower expression in LUAD tissues than normal tissues. We also found that ATP7B (4%), AOC1 (3%) PDE3B (2%), DβH (2%), CP (1%), ULK2 (1%), PDK1 (1%), LOXL2 (1%) and UBE2D3 (1%) showed higher mutation frequencies. The univariate Cox analysis was used to identify CRGs that have prognostic value. It identified 21 genes that showed significant prognostic value, containing DβH, UBE2D3, SOD1, UBE2D1 and LOXL2. Patients with DβH up-expression have a longer survival time and patients with UBE2D3, SOD1, UBE2D1 and LOXL2 down-expression also have a longer survival time. hsa-miR-29c-3p, hsa-miR-29a-3p, hsa-miR-181c-5p, hsa-miR-1245a, etc., play an important role in the miRNA regulatory network, and in LUAD, miR-29a, miR-29c and miR-181c high expression survival was longer, and miR-1245a low expression survival was longer. We also performed an analysis to examine the relationships between DβH, LOXL2, SOD1, UBE2D1 and UBE2D3 and immune infiltration in LUAD, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and DCs.

Conclusion: DβH, UBE2D3, SOD1, UBE2D1, and LOXL2 are potential candidates implicated in LUAD and can be further explored for their application as diagnostic, prognostic, and therapeutic biomarkers for LUAD.