Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Rapid identification of prognostic imaging biomarkers for non-small cell lung cancer by leveraging public gene expression microarray data

ABSTRACT: To rapidly identify new prognostic imaging biomarkers, we propose a bioinformatics approach that integrates gene expression and image data and leverages public gene expression data. We demonstrate our approach in non-small cell lung carcinoma patients for whom CT, PET/CT and gene expression data are available but without clinical follow-up. We extracted 180 image features and 56 high quality gene expression clusters, represented by metagenes. 115 image features were expressed in terms of metagenes, using sparse linear regression and cross-validation, with an accuracy of 65-86%. After mapping the signatures to a public gene expression dataset, 26 image features were significantly associated with recurrence-free survival and 22 with overall survival. A multivariate analysis identified multiple image features that were prognostic, independent of clinical covariates. Identifying prognostic imaging biomarkers by linking images and gene expression with outcomes in public gene expression datasets promises to accelerate the role of imaging in personalized medicine. We studied 26 cases of NSCLC with both PET/CT and microarray data under IRB approval from Stanford University and the Veterans Administration Palo Alto Health Care System. The collection of tissue samples consisted of a distribution of poorly- to well-differentiated adenocarcinomas and squamous cell cancers. The surgeon had removed necrotic debris during excision and sampled cavitary lesions to include as much solid component as practical. Then, from the excised tumor, he cut a 3 to 5 mm thick slice along its longest axis, and froze it within 30 minutes of excision. We retrieved the frozen tissue and extracted the RNA that was then processed by the Stanford Functional Genomics Facility using Illumina Whole Genome Bead Chips (Human HT-12 v3.0)

ORGANISM(S): Homo sapiens

SUBMITTER: Olivier Gevaert

PROVIDER: E-GEOD-28827 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The feasibility of longitudinal metastatic biopsies for gene expression profiling in breast cancer is unexplored. Dynamic changes in gene expression can potentially predict efficacy of targeted cancer drugs. Patients enrolled in a phase III trial of metastatic breast cancer with sunitinib combined with docetaxel (SU+DOC) versus docetaxel alone (DOC) were offered to participate in a translational substudy comprising longitudinal fine needle aspiration biopsies (FNAB) and positron emission imaging before (T1) and two weeks after start of treatment (T2). Aspirated tumor material was used for microarray analysis, and treatment-induced changes (T2 versus T1) in gene expression and standardized uptake values were investigated. Twenty-one patients were included in the docetaxel ± sunitinib trial at Karolinska and 18 of them agreed to participate in the substudy. Of the 18 women enrolled, 8 were randomly assigned to SU+DOC and 10 to DOC. Metastatic FNAB were carried out in 17 of the 18 patients at both time points with no complications reported. Representative tumor material, sufficient for RNA extraction was obtained in 15 patients at T1 and 14 patients at T2. Matched samples both at T1 and T2 were obtained for 14 subjects, 7 in each arm. The main objective was to determine whether gene expression profiling is feasible using sequential, intra-patient FNAB. Secondary objectives were to identify potential biomarkers of early response by gene expression and/or functional imaging and to explore drug action in vivo by changes in gene expression. A Karolinska substudy of the docetaxel ± sunitinib phase III clinical trial utilising sequential metastatic fine needle aspiration biopsies (FNAB) and 18-F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT). In brief, the randomized docetaxel ± sunitinib trial compared sunitinib combined with docetaxel (SU+DOC) versus docetaxel alone (DOC), as first line therapy in patients with HER2 negative metastatic breast cancer. Patients in the exploratory substudy were subjected to baseline FDG PET/CT assessment, followed by FNAB of one tumor lesion prior to start of treatment (Time point T1). FDG PET/CT and FNAB were repeated at Day 14 ± 1 (Time point T2) when sunitinib has achieved steady state.

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Rapid identification of prognostic imaging biomarkers for non-small cell lung cancer by leveraging public gene expression microarray data

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