ODAM: A Novel Tumor Suppressor Silenced in Breast Cancer
ODAM as a Tumor Suppressor in Breast Cancer
DOI:
https://doi.org/10.29409/k7h78q03Keywords:
AKT, Breast Cancer, Kaplan-Meier, ODAMAbstract
Background: The Odontogenic, Ameloblast-Associated gene (ODAM) encodes a matricellular protein that is involved in cell adhesion and odontogenesis. Emerging evidence suggests a role in tumor biology, with its expression documented in various epithelial malignancies, including breast cancer (BC). This study investigated the expression, clinical significance, and functional role of ODAM in BC, with a focus on its relationship with the AKT signaling pathway.
Methods: ODAM expression in malignant, benign, and control groups (n=35 per group) was quantified via quantitative real-time PCR (qRT‒PCR) and normalized to that of the housekeeping gene GAPDH. Patient classification and dataset generation were based on oncologist evaluations and confirmed mammography findings. Serum AKT concentrations were measured by ELISA. Survival analysis was performed using a large public breast cancer dataset.
Results: ODAM expression was significantly downregulated in malignant breast tissue samples than in benign and control tissue samples, with an approximately 66.6-fold downregulation in ODAM expression in BC patients (p<0.01). This loss of ODAM was inversely correlated with serum AKT levels, which were significantly elevated in malignant patients (3.173 ng/ml) versus controls (1.510 ng/ml; p<0.01). ODAM overexpression in aggressive BC cells suppressed tumorigenic properties by inhibiting growth, migration, and invasion while promoting cell adhesion and apoptosis. Mechanistically, ODAM may be associated with alterations in serum AKT and PI3K/AKT signaling and the upregulation of the expression of the tumor suppressors phosphatase and tensin PTEN. Critically, Kaplan-Meier survival analysis revealed that high ODAM expression is a favorable prognostic biomarker and is associated with significantly improved overall survival in BC patients (HR = 0.89; 95% CI = 0.80–0.98; p = 0.022).
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Data Availability Statement
The raw data supporting the findings of this study, including the raw qRT‒PCR and ELISA datasets, are available from the corresponding author upon reasonable request.
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