Abstract
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common lung cancer, associated with high metastasis and low survival rates. Identifying reliable biomarkers is essential for better prognosis and treatment. METHODS: In this study, we analyzed RNA sequencing data, mutation information, and clinical data from the TCGA-LUAD cohort and other multicenter datasets to investigate the role of Holliday junction recognition protein (HJURP) in LUAD. We employed immunohistochemistry in tissue microarray cohort to validate the prognostic significance of HJURP. The DepMap project was used to validate the effect of HJURP knockout in vitro. RESULTS: Holliday junction recognition protein was identified as an adverse prognostic factor in the TCGA-LUAD cohort and diverse ethnic groups. Its expression correlated with poor immunotherapy outcomes, and HJURP knockout suppressed cancer cell proliferation. High HJURP expression was linked to increased mutation frequency, particularly in TP53 and TTN. Pan-cancer analysis also indicated HJURP as a poor prognostic factor in various solid tumors. CONCLUSIONS: Holliday junction recognition protein emerges as a significant biomarker in LUAD, consistently associated with poor prognosis across multiple cohorts. Its role in various oncogenic pathways and correlation with advanced disease stages underscore the potential of HJURP as a target for therapeutic intervention and as a marker for prognosis in LUAD.