• ORC6 identified as hub biomarker via machine learning. • ORC6 overexpression correlates with poor LUAD prognosis. • ORC6 linked to immunosuppressive tumor microenvironment. • ORC6 expression predicts resistance to immunotherapy. The origin recognition complex (ORC) is a DNA-binding complex composed of six subunits involved in DNA replication in cancer cells. The prognostic and immunological implications of ORC6 in lung adenocarcinoma (LUAD) are not yet clear. This study utilizes multiple databases (such as TCGA, GEO, GTEx, etc.) to investigate the potential significance of ORC6 in LUAD. The results show that high ORC6 expression is associated with advanced disease and poorer prognosis and is involved in biological processes such as cell cycle regulation, DNA replication, and signal transduction. The expression of ORC6 correlates negatively with the infiltration of CD4+ and CD8+ T cells but positively with the infiltration of cancer-associated fibroblasts and endothelial cells. Additionally, a positive correlation between ORC6 and immunosuppression-related genes (such as LAG3 and PDCD1) was found. Validation of ORC6 expression was conducted through qRT-PCR, western blotting, and immunofluorescence, indicating its potential diagnostic, prognostic, and therapeutic value in LUAD.
Huang et al. (Mon,) studied this question.