Prospective technical validation and assessment of intra-tumour heterogeneity of a low density array hypoxia gene profile in head and neck squamous cell carcinoma.
Authors
Betts, Guy N JEustace, Amanda
Patiar, S
Valentine, Helen R
Irlam, Joely J
Ramachandran, A
Merve, Ashriwad
Homer, Jarrod J
Möller-Levet, Carla S
Buffa, F
Hall, G
Miller, Crispin J
Harris, A
West, Catharine M L
Affiliation
Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, Christie Hospital, Wilmslow Road, Manchester M20 4BX, United Kingdom.Issue Date
2012-08-27
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BACKGROUND AND PURPOSE: Tumour hypoxia is associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC), however there is no accepted method for assessing hypoxia clinically. We aimed to conduct a technical validation of a hypoxia gene expression signature using the TaqMan Low Density Array (TLDA) platform to investigate if this approach reliably identified hypoxic tumours. MATERIALS AND METHODS: Tumour samples (n=201) from 80 HNSCC patients were collected prospectively from two centres. Fifty-three patients received pimonidazole prior to surgery. TaqMan Low Density Array-Hypoxia Scores (TLDA-HS) were obtained by quantitative real-time PCR (qPCR) using a 25-gene signature and customised TLDA cards. Assay performance was assessed as coefficient of variation (CoV). RESULTS: The assay was sensitive with linear reaction efficiencies across a 4log(10) range of inputted cDNA (0.001-10ng/μl). Intra- (CoV=6.9%) and inter- (CoV=2.0%) assay reproducibility were excellent. Intra-tumour heterogeneity was lower for TLDA-HS (23.2%) than for pimonidazole (67.2%) or single gene measurements of CA9 (62.2%), VEGFA (45.0%) or HIG2 (39.4%). TLDA-HS in HNSCC cell lines increased with decreasing pO(2). TLDA-HS correlated with Affymetrix U133 Plus 2.0 microarray HS (p<0.01) and positive pimonidazole scores (p=0.005). CONCLUSIONS: Gene expression measurements of hypoxia using a 25-gene signature and TLDA cards are sensitive, reproducible and associated with lower intra-tumour heterogeneity than assaying individual genes or pimonidazole binding. The approach is suitable for further assessment of prognostic and predictive capability in clinical trial material.Citation
Prospective technical validation and assessment of intra-tumour heterogeneity of a low density array hypoxia gene profile in head and neck squamous cell carcinoma. 2012: Eur J CancerJournal
European Journal of CancerDOI
10.1016/j.ejca.2012.07.028PubMed ID
22951015Type
ArticleLanguage
enISSN
1879-0852ae974a485f413a2113503eed53cd6c53
10.1016/j.ejca.2012.07.028
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