Serum CD44 Variant 6 to CD44 Ratio and Vascular Endothelial Growth Factor Levels as Predictors of Metastasis in Luminal Subtype Breast Cancer

Ni Putu Yenny Kendarini (Division of General Surgery, Balimed Hospital, Jl. Mahendradatta No.57 X, Denpasar, Bali 80119)
Ida Bagus Tjakra Wibawa Manuaba (Division of Surgical Oncology, Prima Medika Hospital, Jl. Raya Sesetan No.10, Denpasar, Bali 80223)
I Wayan Sudarsa (Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Universitas Udayana/Prof. dr. I.G.N.G. Ngoerah General Hospital, Jl. P.B. Sudirman, Denpasar, Bali 80232)
Tjokorda Gde Bagus Mahadewa (Department of Neurosurgery, Faculty of Medicine, Universitas Udayana/Prof. dr. I.G.N.G. Ngoerah General Hospital, Jl. P.B. Sudirman, Denpasar, Bali 80232)
Ni Nyoman Ayu Dewi (Department of Biochemistry, Faculty of Medicine, Universitas Udayana/Prof. dr. I.G.N.G. Ngoerah General Hospital, Jl. P.B. Sudirman, Denpasar, Bali 80232)
Prayuda Prayuda (Division of Internal Medicine, Balimed Hospital, Jl. Mahendradatta No.57 X, Denpasar, Bali 80119)
Putu Febry Krisna Pertiwi (Faculty of Medicine, Universitas Udayana, Jl. P.B. Sudirman, Denpasar, Bali 80232)

The Indonesian Biomedical Journal
Vol 17, No 3 (2025)

BACKGROUND: Metastasis is the leading cause of mortality in luminal subtype breast cancer. While cluster of differentiation (CD)44 has been widely studied, the prognostic relevance of its isoforms particularly the CD44v6/CD44s ratio remains unclear. This study evaluates CD44v6, CD44s, vascular endothelial growth factor (VEGF), and the CD44v6/CD44s ratio as potential prognostic biomarkers for metastasis in luminal breast cancer.METHODS: This case-control study included 38 luminal subtype breast cancer patients (18 with metastasis, 20 without metastasis). Serum levels of CD44v6, CD44s, VEGF, and the CD44v6/CD44s ratio were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Statistical analyses included ROC analysis to determine optimal cut-off points, logistic regression to assess risk factors, and correlation analysis for biomarker relationships.RESULTS: A low CD44v6/CD44s ratio (<0.03) was identified as a significant independent factor for metastasis (adjusted OR 7.0, 95% CI: 1.2–40.6, p=0.03). While serum levels of CD44v6, CD44s, and VEGF were higher in the metastasis group, these individual markers showed a non-significant trend toward association with metastasis. A strong positive correlation was observed between CD44s and VEGF levels (r=0.7, p<0.01).CONCLUSION: The CD44v6/CD44s ratio showed a significant association with metastasis and may have potential as a prognostic marker in luminal breast cancer. Further studies with larger sample sizes are needed to confirm these findings.KEYWORDS: CD44v6, CD44s, VEGF, CD44v6/CD44s ratio, luminal breast cancer, metastasis