Objectives: C1QBP is a multi-compartmental protein implicated in diverse cellular processes. However, its clinical predictive value, particularly its association with immune cell infiltration, in lung adenocarcinoma (LUAD) remains unelucidated. Thus, the present study aimed to comprehensively evaluate C1QBP expression patterns, prognostic significance, and its correlation with the tumor immune microenvironment (TIME) in LUAD. Methods: We first assessed C1QBP expression levels and prognostic relevance in LUAD using multiple bioinformatics platforms. Subsequently, we analyzed the associations of C1QBP expression with immune cell infiltration and immunotherapeutic response, and identified signaling pathways linked to C1QBP expression via Gene Set Enrichment Analysis (GSEA). Finally, enzyme-linked immunosorbent assay (ELISA) was employed to validate the correlation between serum C1QBP concentration and prognosis in non-small cell lung cancer (NSCLC) patients receiving immunotherapy. Results: C1QBP was highly expressed in LUAD tissues, and this high expression was significantly associated with advanced tumor stage. Moreover, high C1QBP expression emerged as an independent risk factor for overall survival (OS) in LUAD patients. Bioinformatics analyses revealed that C1QBP expression was negatively correlated with the infiltration levels of multiple immune cell subsets (including T cells, B cells, and dendritic cells) in LUAD, while patients with low C1QBP expression exhibited higher Immunophenoscore (IPS). GSEA further demonstrated that high C1QBP expression was positively correlated with pathways regulating the tumor cell cycle, but negatively correlated with immune-related signaling pathways. Finally, in NSCLC patients treated with immune checkpoint inhibitors (ICIs), those with higher serum C1QBP concentrations had significantly shorter OS and progression-free survival (PFS). Conclusions: Our study identifies C1QBP as a potential oncogene that is closely associated with the TIME in LUAD. Collectively, these findings suggest that C1QBP holds promise as a novel indicator of poor prognosis in LUAD patients.
Zhang et al. (Sun,) studied this question.