SLC7A3 Expression Is Associated With Migration, Invasion, and Survival in Oral Squamous Cell Carcinoma.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with limited prognostic biomarkers, in which metabolic reprogramming contributes to tumor progression. Amino acid transporters of the solute carrier family have emerged as key regulators of cancer biology; however, the role of solute carrier family 7 member 3 (SLC7A3), a cationic amino acid transporter involved in arginine uptake, remains poorly characterized in OSCC.

Methods: SLC7A3 expression was evaluated using RNA expression data from the Cancer Genome Atlas OSCC cohort (TCGA-OSCC), and protein levels were assessed by immunohistochemistry in a tissue microarray comprising 67 OSCC samples matched with normal oral tissue and 18 metastatic lymph nodes. Associations with clinicopathological features and survival were analyzed using chi-squared tests, Kaplan-Meier curves, and Cox regression. Functional assays, including cell cycle, apoptosis, migration, and invasion analyses, were performed in HSC3 cells following SLC7A3 knockdown.

Results: In TCGA-OSCC, SLC7A3 mRNA levels were significantly lower in tumors than in nontumor tissues (p = 0.017), with no association with disease-specific or disease-free survival. At the protein level, SLC7A3 was significantly upregulated in tumors (p = 0.007), and high expression was associated with early clinical stage (p = 0.007) and improved disease-specific survival, remaining significant in multivariate Cox analysis (HR: 0.18, 95% CI: 0.07-0.50, p = 0.001). Functionally, SLC7A3 knockdown did not alter cell cycle distribution or apoptosis but significantly increased OSCC cell migration and invasion.

Conclusion: High SLC7A3 protein levels were associated with OSCC cell migration and invasion and improved disease-specific survival, suggesting its potential as an indicator of tumor aggressiveness and a promising prognostic potential.