Association between hypoxic volume and underlying hypoxia-induced gene expression in oropharyngeal squamous cell carcinoma.
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 with64Cu-ATSM PET/CT.


METHODS
64Cu-ATSM imaging, molecular and clinical data were obtained for 15 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 SUVmaxand 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). Sixteen genes were positively and five 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.


CONCLUSIONS
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.
Department of Molecular Oncology, King's College London, Hodgkin Building, London SE1 1UL, UK.
Yae-Eun
YE
Suh
Institute of Mathematical and Molecular Biomedicine, King's College London, Guy's Medical School Campus, London SE1 1UL, UK.|Richard Dimbleby Department of Cancer Research, Randall Division and Division of Cancer Studies, King's College London, Guy's Medical School Campus, London SE1 1UL, UK.
Katherine
K
Lawler
Department of Oral Pathology, King's College London, Guy's Hospital, London SE1 9RT, UK.
Rhonda
R
Henley-Smith
PET Imaging Centre, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St Thomas' Hospital, London SE1 7EH, UK.
Lucy
L
Pike
Radcliffe Department of Medicine, Nuffield Division of Laboratory Science, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Russell
R
Leek
PET Imaging Centre, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St Thomas' Hospital, London SE1 7EH, UK.
Sally
S
Barrington
Department of Oral Pathology, King's College London, Guy's Hospital, London SE1 9RT, UK.
Edward W
EW
Odell
Richard Dimbleby Department of Cancer Research, Randall Division and Division of Cancer Studies, King's College London, Guy's Medical School Campus, London SE1 1UL, UK.|Breakthrough Breast Cancer Research Unit, Department of Research Oncology, Guy's Hospital, King's College London School of Medicine, London SE1 9RT, UK.|UCL Cancer Institute, Paul O'Gorman Building, University College London, London WC1E 6DD, UK.
Tony
T
Ng
Radcliffe Department of Medicine, Nuffield Division of Laboratory Science, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Francesco
F
Pezzella
Department of Clinical Oncology, Guy's and St Thomas' Hospital NHS Foundation Trust, Guy's Hospital, London SE1 9RT, UK.
Teresa
T
Guerrero-Urbano
Department of Molecular Oncology, King's College London, Hodgkin Building, London SE1 1UL, UK.
Mahvash
M
Tavassoli
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D003301:Copper Radioisotopes / Q000378:metabolism; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013882:Thiosemicarbazones / Q000378:metabolism; D059467:Transcriptome
D014408:Biomarkers, Tumor; D003301:Copper Radioisotopes; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones