ALDOB is a prognostic biomarker and a potential immunotherapy target for clear cell renal cell carcinoma

Background Aldolase B (ALDOB), functioning as a glycolytic enzyme, exhibits a controversial role in malignancies and demonstrates dual potential as both a tumor suppressor and cancer-promoting enzyme. Nevertheless, it is still uncertain if there is a relationship between ALDOB levels, prognosis, and...

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Main Authors: Wu Xu, Dali Wu, Cuilian Li, Lingfei Yan, Bo Peng, Yang Luo, Dawei Liu, Qing Li, Tao Wang
Format: Article
Language:English
Published: PeerJ Inc. 2025-08-01
Series:PeerJ
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Online Access:https://peerj.com/articles/19869.pdf
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Summary:Background Aldolase B (ALDOB), functioning as a glycolytic enzyme, exhibits a controversial role in malignancies and demonstrates dual potential as both a tumor suppressor and cancer-promoting enzyme. Nevertheless, it is still uncertain if there is a relationship between ALDOB levels, prognosis, and tumor-infiltrating lymphocytes in clear cell renal cell carcinoma (ccRCC). Objective This study aims to investigate the prognostic significance of ALDOB in ccRCC and its potential association with clinicopathological features and tumor immune microenvironment. By integrating multi-database bioinformatics analysis and experimental validation, we seek to elucidate the role of ALDOB in ccRCC progression and its potential as a predictive biomarker. Methods To ascertain the potential link between ALDOB level, clinical parameters, and overall survival (OS) in individuals with ccRCC, we employed diverse databases, which include The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Human Protein Atlas (HPA) and The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN). Furthermore, an in-depth analysis of the link between tumor-infiltrating immune cells (TIIC) and ALDOB was carried out using the TIMER database. Immunohistochemistry (IHC) was applied to identify the ALDOB level in a tissue microarray. Results The expression of ALDOB demonstrated a strong association with pathologic T stage, pathologic N stage, pathologic M stage, histologic grade, and gender. Decreased ALDOB level was linked to unfavorable disease-specific survival (DSS), progress free interval (PFI), and OS outcomes (p < 0.001). Subsequently, a marked link was observed between ALDOB level and a heightened presence of infiltrating Treg, Th17 cells, and neutrophils in ccRCC. IHC showed that the ALDOB level in ccRCC samples was notably diminished relative to that in the adjacent normal tissues. Conclusions As a prospective predictive indicator for individuals with ccRCC, reduced ALDOB level exhibited strong correlations with clinical characteristics, unfavorable outcomes, and immune infiltration in individuals with ccRCC.
ISSN:2167-8359