Increased Expression of Hypoxia-inducible Factor 1 alpha and its Impact on Transcriptional Changes and Prognosis in Malignant Tumours of the Ocular Adnexa

Methods: We included 49 subjects with malignant tumours (25 squamous cell carcinomas (SCC), 15 non-Hodgkin lymphomas, 9 melanomas) and 30 patients with benign tumours of the ocular adnexa (13 papillomas, 7 reactive lymphoid hyperplasias (RLHs) and 10 nevi) as controls. We quantified HIF-1α protein expression by immunohistochemistry and assessed the association between HIF-1α and clinical outcome via Kaplan-Meier analysis. Furthermore, we assessed the expression of HIF-1α downstream factors by transcriptional sequencing using the massive analysis of cDNA ends (MACE) technology. Results: SCCs revealed a strong HIF-1α expression in 61% of tumour cells in comparison to only 22% in papillomas (p < 0.0001). In contrast, malignant melanomas and lymphomas revealed a similar HIF-1α expression compared to nevi and RLHs. Transcriptional sequencing and Gene Ontology Cluster analysis demonstrated 37 hypoxia-associated factors, including HIF-1α, VEGF, SFRP1 and LOXL2 that are significantly increased in SCC and may contribute to tumour proliferation, angiogenesis, and metastasis. Association analysis between HIF-1α immunoreactivity and clinical outcome revealed a trend towards an unfavorable prognosis in malignant tumours with increased HIF-1α expression. Conclusions: HIF-1α protein is increased in malignant tumours of the ocular adnexa, which is associated with an increase in multiple HIF-1α-downstream factors and a trend towards an unfavorable clinical outcome.

Ansprechpartner: Clemes Lange

Projektbeginn: 2011
Projektende: 2017

Clemes Lange

Albert-Ludwigs-Universität Freiburg
Augenklinik
Abteilung Allgemeine Augenheilkunde mit Poliklinik
Killianstrasse 5
79106 Freiburg

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