Abstract 757P
Background
Retinoblastoma (Rb) is the most common intraocular malignancy of childhood. In normoxia condition, hypoxia inducible factors (HIF-1α, HIF-2α, HIF-3α) and prolyl hydroxylase domains (PHD1, PHD2 and PHD3) together function as an oxygen sensor. The primary oxygen sensor in cells is PHD2, which is responsible for stabilizing HIF-1α under normoxia. HIF-1α regulates hypoxia-mediated apoptosis, cell proliferation and tumor angiogenesis. Therefore, the aim of this study was to explore the expression level of hypoxia in the regulation of oxygen sensing enzyme in Rb patients.
Methods
This prospective study includes a total of 45 cases which includes 30 primary (group I) and 15 chemoreduced (group II) retinoblastoma patients. mRNA expression level of HIF-1α, HIF-2α, HIF-3α and PHD1, PHD2 and PHD3 gene was investigated using quantitative Real-time PCR (qRT-PCR). Statistical analysis was performed to correlate their expression with clinicopathological parameters and patient outcome.
Results
Twenty-four percent patients exhibited advanced tumor staging with a male preponderance (75%). Massive choroidal invasion and retrolaminar optic-nerve invasion was observed in 18% and 12% cases, respectively. The mRNA expression of HIF-1α, HIF-2α, HIF-3α was found to be upregulated in 60%, 53.3%, and 63.3% cases, respectively, while PHD1, PHD2 and PHD3 was downregulated in 88%, 90% and 83.3% cases, respectively. On statistical analysis, patients with massive choroidal invasion were statistically significant with HIF-1α expression (p=0.001), whereas optic nerve retrolaminar invasion statistically correlated with PHD1 and PHD2 expression (p=0.015).
Conclusions
This study highlights the dysregulation of the oxygen-sensing pathway in retinoblastoma. Elevated HIF-1α and decreased PHD1 expression were associated with histopathological high-risk features, suggesting their potential role in disease progression. Targeting this signaling pathway may hold promise for future therapeutic strategies in retinoblastoma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Indian Council of Medical Research.
Disclosure
All authors have declared no conflicts of interest.