Objectives: This study aims to elucidate the role of cAMP responsive element binding protein 3 like 4 (CREB3L4) in the pathogenesis of lung adenocarcinoma (LUAD) and to provide new insights and approaches for its effective treatment. An analysis was conducted on the expression and prognostic implications of CREB3L4 in LUAD.
Methods: Potential downstream target genes regulated by CREB3L4 were identified through chromatin immunoprecipitation assay sequencing and mRNA sequencing analyses, and the regulatory relationship, mechanism, and prognostic significance of the identified target gene in LUAD were subsequently confirmed. Moreover, immune microenvironment analysis, the identification of immunotherapy targets, and chemotherapy drug sensitivity analyses were performed for LUAD with different levels of CREB3L4 expression.
Results: CREB3L4 is upregulated in LUAD and is significantly associated with tumor staging and poor prognosis, influencing cell proliferation and migration. Comprehensive analysis through chromatin immunoprecipitation assay sequencing and mRNA sequencing highlighted RAS and EF-hand domain containing (RASEF) as a potential target gene under the regulation of CREB3L4, which was found to be overexpressed in LUAD and linked to tumor staging, as well as cell proliferation and migration. Notably, the knockdown of CREB3L4 markedly reduced RASEF promoter-driven luciferase activity. The aberrant expression of CREB3L4 in LUAD was intricately related to the complex tumor microenvironment and immune therapy targets, including PD-L1, CTLA-4, CD28, CD80, and demonstrated increased sensitivity to chemotherapy drugs such as osimertinib, gefitinib, and afatinib.
Conclusions: These findings provide preliminary evidence for the involvement of the CREB3L4/RASEF signaling pathway in LUAD pathogenesis and suggest its potential as a novel biomarker for accurate diagnosis and targeted therapy.
Keywords: CREB3L4; Lung adenocarcinoma; RASEF; biomarker; signaling pathway.
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