Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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 patientâs risk of failure and allocate high risk patients to adjuvant hypoxia-targeted therapy. Total 150 patient and 2 cell line samples were analysed with Illumina WG-6, while 136 patient and 6 cell line samples were analyzied with Illumina HT-12.

ORGANISM(S): Homo sapiens

SUBMITTER: Heidi Lyng

PROVIDER: E-GEOD-72723 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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.

Fjeldbo Christina S CS Julin Cathinka H CH Lando Malin M Forsberg Malin F MF Aarnes Eva-Katrine EK Alsner Jan J Kristensen Gunnar B GB Malinen Eirik E Lyng Heidi H

Clinical cancer research : an official journal of the American Association for Cancer Research 20160324 16

<h4>Purpose</h4>A 31-gene expression signature reflected in dynamic contrast enhanced (DCE)-MR images and correlated with hypoxia-related aggressiveness in cervical cancer was identified in previous work. We here aimed to construct a dichotomous classifier with key signature genes and a predefined classification threshold that separated cervical cancer patients into a more and less hypoxic group with different outcome to chemoradiotherapy.<h4>Experimental design</h4>A training cohort of 42 patie ...[more]

PMID: 27012812

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Project description:We aimed to investigate the transcriptional program associated with pimonidazole staining in prostate cancer. A pimonidazole gene signature was identified that showed positive correlation to Ki67 labeling index, indicating increased proliferation in pimonidazole positive tumors. A positive correlation to clinical tumor stage and presence of lymph node metastasis was also found, consistent with associations between pimonidazole staining and clinico-pathological parameters. Moreover, the gene signature was associated with high Gleason score in a validation cohort of 59 patients and showed prognostic impact independent of Gleason score and other clinical markers in a watchful waiting validation cohort of 281 patients. Our work reveals the molecular basis of an aggressive prostate cancer phenotype reflected by pimonidazole staining, and suggests that genes involved in proliferation, DNA repair and hypoxia response contribute to this phenotype. We combined pimonidazole immunohistochemistry data and expression profiles to identify transcriptional program activated in pimonidazole positive tumors. Whole-genome gene expression profiles were determined in tumor biopsies from an investigation cohort of 46 patients, where 39 patients had received pimonidazole prior to surgery. Gene ontology analysis of 1046 genes upregulated in pimonidazole positive tumors, as defined by a staining fraction above 10%, showed significant enrichment of the biologic processes cell cycle, translation and cellular response to stress. Gene set analysis based on this result identified gene expressions in proliferation, DNA repair and hypoxia response as major parts of the transcriptional program associated with pimonidazole staining. Gene expression data of four prostate cancer cell lines were used to generate hypoxia response gene sets for this analysis. A signature of the 32 most essential genes in the program was constructed and shown to be associated with prostate cancer aggressiveness in two independent validation cohorts.

Dataset Information

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

Publications

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.

Similar Datasets

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