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Integrative analysis of DCE-MRI and gene expression profiles in construction of a gene classifier for assessment of hypoxia-related risk of chemoradiotherapy failure in cervical cancer

ABSTRACT: We have previously identified a prognostic 31-gene expression signature in locally advanced cervical cancer that is associated with tumor hypoxia and reflected by the dynamic contrast enhanced magnetic resonance (DCE-MR) image parameter ABrix. To bring the signature closer to clinical use, we here aimed to construct a classifier with key signature genes that retained an association to ABrix and separated the patients into groups with different hypoxia status and chemoradiotherapy outcome. A training cohort of 42 patients and two independent cohorts of 108 and 131 patients were included. Gene expression data were generated from tumor biopsies by two Illumina array generations (WG6, HT12), and for a subset of 74 patients, by the RT-qPCR platform. The amplitude ABrix in the Brix pharmacokinetic model was extracted from DCE-MR images of 64 patients and used as a measure of hypoxia. Different classifiers were constructed in the training cohort. By evaluating their ability to separate the patients correctly according to ABrix, a 6-gene classifier with strong correlation to ABrix was identified. In validation analyses, the classifier separated the patients into two groups with 5-years progression-free survival probabilities of 85% and 60%. Both the prognostic value and ABrix-association were confirmed in an independent cohort, and robustness across array generations and assay platforms was demonstrated. The prognostic value was independent of existing clinical markers. A robust, prognostic hypoxia classifier has been constructed, and might be used alone or combined with DCE-MR imaging to achieve an early indication of a patient’s risk of failure and allocate high risk patients to adjuvant hypoxia-targeted therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE72723 | GEO | 2016/03/29

SECONDARY ACCESSION(S): PRJNA294765

REPOSITORIES: GEO

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Integrative analysis of DCE-MRI and gene expression profiles in construction of a gene classifier for assessment of hypoxia-related risk of chemoradiotherapy failure in cervical cancer

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