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Association between hypoxic volume and underlying hypoxia-induced gene expression in oropharyngeal squamous cell carcinoma (OPSCC): Hypoxia biomarkers from 64Cu-ATSM PET/CT imaging

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)1057–1064
JournalBritish Journal of Cancer
Volume116
DOIs
Accepted/In press20 Feb 2017
Published21 Mar 2017

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Abstract

Background: Hypoxia imaging is a promising tool for targeted therapy but the links between imaging features and underlying molecular characteristics of the tumour have not been investigated. The aim of this study was to compare hypoxia biomarkers and gene expression in oropharyngeal squamous cell carcinoma (OPSCC) diagnostic biopsies with hypoxia imaged with 64Cu-ATSM PET/CT. Methods: 64Cu-ATSM imaging, molecular and clinical data were obtained for patients. Primary tumour SUVmax, tumour to muscle ratio (TMR) and hypoxic volume were tested for association with reported hypoxia gene signatures in diagnostic biopsies. A putative gene signature for hypoxia in OPSCCs (hypoxic volume-associated gene signature, HVS) was derived. Results: Hypoxic volume was significantly associated with a reported hypoxia gene signature (rho=0.57, P=0.045), but SUVmax and TMR were not. Immunohistochemical staining with the hypoxia marker carbonic anhydrase 9 (CA9) was associated with a gene expression hypoxia response (rho=0.63, P=0.01). 16 genes were positively and 5 genes negatively associated with hypoxic volume (adjusted P<0.1; eight genes had adjusted P<0.05; HVS). This signature was associated with inferior 3-year progression-free survival(HR=1.5 [1.0-2.2], P=0.047) in an independent patient cohort. Conclusion: 64Cu-ATSM defined hypoxic volume was associated with underlying hypoxia gene expression response. A 21-gene signature derived from hypoxic volume from patients with OPSCCs in our study may be linked to progression-free survival.

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