PDGF, NGF, and EGF as main contributors to tumorigenesis in high-risk retinoblastoma

Karim Al-Ghazzawi; Michael Wessolly; Sami Dalbah; Petra Ketteler; Tobias Kiefer; Nikolaos Bechrakis; Jabbarli Leyla; Saskia Ting; Eva Biewald; Fabian D Mairinger

doi:10.3389/fonc.2023.1144951

PDGF, NGF, and EGF as main contributors to tumorigenesis in high-risk retinoblastoma

Front Oncol. 2023 Oct 30:13:1144951. doi: 10.3389/fonc.2023.1144951. eCollection 2023.

Affiliations

¹ Department of Ophthalmology, University Hospital Essen, Essen, Germany.
² Department of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
³ Department of Pediatric Hematology and Oncology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁴ Institute of Pathology Nordhessen, Kassel, Germany.

Abstract

Retinoblastoma (RB) is the most common form of eye cancer experienced in childhood. Its aggressive malignancy is associated with excellent survival rates in high-income countries; however, the prognosis in third-world countries is less favorable. Early diagnosis can maximize the patient's visual outcomes and their survival rate. Therapy should be conducted in highly specialized treatment centers. Intravenous chemotherapy (IVC) in bilaterally affected children currently forms the majority of therapy. Local destructive procedures and local chemotherapies such as intra-arterial chemotherapy (IAC) or intravitreal chemotherapy can be taken into consideration depending on the extent and size of the tumor. Nonetheless, children and parents remain under constant stress, revisiting doctors for medical treatment and fearing vision loss and even enucleation of the eye. Adequate molecular patient stratification to improve targeted therapy is still lacking. This retrospective study analyzed formalin-fixed paraffin-embedded specimens from a cohort of 21 RB samples. A total of 11 of those samples showed undifferentiated retinoblastoma (URB) histopathological risk features, and the other 10 showed differentiated retinoblastoma (DRB) histopathological grading. RNA from all samples was isolated and analyzed via digital gene expression patterns. Conductors of cell survival and DNA repair were dominant in the DRB samples. In contrast, the agents responsible for cell-cycle progression and apoptosis were overexpressed in URB samples. Our work reveals the importance of molecular mechanisms within the immune system subjected to histologic subtypes of RB, providing more detailed background on their genetic behavior. This is of great interest for therapeutic strategies, such as targeted immune- and gene-based therapies, for retinoblastoma.

Keywords: MAPK/ERK2 pathway 1; PDGF = platelet-derived growth factor; biomarkers; growth factors (angiogenesis factors); pediatric cancer and oncology; retinoblastoma; retinoblastoma - epigenetics; targeted therapy.