Photo Credit: Nadzeya Haroshka

The following is a summary of “Prognostic implications of HIF-1α expression in anal squamous cell carcinoma treated with intensity-modulated radiotherapy (IMRT),” published in the September 2024 issue of Oncology by Mohamed et al.

Hypoxia-inducible factor-1α (HIF-1α) is a pivotal transcription factor activated in response to hypoxic conditions, playing a central role in the regulation of genes that drive tumor survival, progression, and therapeutic resistance. This study aimed to assess the prognostic significance of HIF-1α expression in patients with anal squamous cell carcinoma (ASCC) undergoing chemoradiation therapy. A retrospective analysis was conducted on 28 patients with ASCC treated with intensity-modulated radiotherapy (IMRT) at the center between 2009 and 2022. HIF-1α expression was evaluated using immunohistochemistry on formalin-fixed, paraffin-embedded tissue samples. Quantitative analysis of HIF-1α levels was performed, and their correlation with clinical outcomes—namely, disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and overall survival (OS)—was examined through Cox regression models. 

Additionally, tissue specimens from 17 patients were analyzed for potential PIK3CA mutations via Sanger sequencing to explore any association with HIF-1α expression. The results revealed that elevated HIF-1α expression was significantly correlated with poorer DFS (p = 0.005), LRRFS (p = 0.012), and OS (p = 0.009), highlighting its potential as a biomarker for adverse outcomes in patients with ASCC undergoing chemoradiation. While HIF-1α expression was marginally higher in males than in females (p = 0.056), no significant associations were found between HIF-1α levels and tumor stage or p16 status. Notably, a positive correlation was observed between body mass index (BMI) and HIF-1α expression (Pearson correlation r = 0.5, p = 0.0084), suggesting a possible link between metabolic status and tumor hypoxia. 

The study also found that only one patient exhibited a PIK3CA mutation, limiting the ability to assess its relationship with HIF-1α expression. In conclusion, the findings underscore the potential of HIF-1α as a prognostic biomarker in ASCC and suggest that metabolic factors, such as BMI, may influence tumor biology through hypoxic pathways. Further research with larger patient cohorts is necessary to confirm these findings and explore targeted therapeutic strategies to modulate HIF-1α activity.

Source: sciencedirect.com/science/article/pii/S2405630824001307