ASSOCIATION OF SERUM HYPOXIA MARKERS (VASCULAR ENDOTHELIAL GROWTH FACTOR, CARBONIC ANHYDRASE IX, AND LACTATE) WITH HYPOXIA-INDUCIBLE FACTOR-1 ALPHA EXPRESSION IN CERVICAL CANCER TISSUES: POTENTIAL IMPLICATIONS FOR TREATMENT RESPONSE AND TARGETED THERAPY
DOI:
https://doi.org/10.22159/ajpcr.2026v19i3.57656Keywords:
Cervical cancer, Tumor hypoxia, HIF-1α,, Serum hypoxia markers (VEGF, CA-IX, and Lactate),, Radiotherapy,, Chemoresistance,, Biomarkers, Therapeutic stratificationAbstract
Objectives: To determine whether circulating serum hypoxia markers (vascular endothelial growth factor [VEGF], carbonic anhydrase IX [CA-IX], and Lactate) are associated with tumor hypoxia-inducible factor-1 alpha (HIF-1α) expression in cervical cancer, and to assess the possible utility of these biomarkers for therapy-oriented risk stratification.
Methods: In this observational study, patients with histopathologically confirmed cervical cancer were enrolled before starting any definitive treatment. Pre-treatment blood samples were analyzed for serum hypoxia markers (VEGF, CA-IX, and Lactate) using validated biochemical assays. HIF-1α expression in tumor tissue was evaluated by immunohistochemistry and graded semi-quantitatively. Relationships between serum marker levels and HIF-1α scores were examined using correlation testing, and comparisons were made across clinicopathological variables relevant to treatment planning.
Results: Patients showing strong HIF-1α expression had significantly higher serum hypoxia marker levels (VEGF, CA-IX, and Lactate) than those with low/absent expression (mean±standard deviation: 8.6±2.1 vs. 5.2±1.7 units; p<0.01). Serum marker levels correlated positively with HIF-1α expression scores (r≈0.58; p<0.001). Elevated biomarker values were more common in advanced disease, with nearly two-thirds of stage III–IV cases demonstrating high HIF-1α expression. Overall, the pattern suggests that higher circulating hypoxia markers may reflect a hypoxia-driven, treatment-resistant tumor phenotype with potential implications for reduced radiotherapy and chemotherapy responsiveness.
Conclusion: Serum hypoxia markers (VEGF, CA-IX, and Lactate) show a significant association with tumor HIF-1α expression in cervical cancer and may act as minimally invasive indicators of a hypoxic microenvironment linked to therapeutic resistance. These biomarkers could aid risk stratification and support personalized treatment approaches, including consideration of treatment intensification and hypoxia-targeted strategies.
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