Molecular bases of morphometric composition in Glioblastoma multiforme

Ju Han, Hang Chang, Gerald V. Fontenay, Paul T. Spellman, Alexander D Borowsky, Bahram Parvin

Research output: Chapter in Book/Report/Conference proceedingConference contribution

3 Scopus citations

Abstract

Integrated analysis of tissue histology with the genome-wide array (e.g., OMIC) and clinical data have the potential for hypothesis generation and be prognostic. OMIC and clinical data are typically characterized and summarized at the patient level while whole mount histological sections are often heterogeneous in terms of nuclear morphology and organization. In this paper, we propose a multilevel framework for summarization and association of morphometric data. At the lowest level, each nucleus is segmented and then profiled with a multi-dimensional representation. At the intermediate level, cellular profiles are summarized within a local neighborhood, and further clustered into subtypes. At the highest level, each patient is represented by the composition of subtypes that are computed from the intermediate level, and then integrated with OMIC and outcome data for further analysis. The framework has been applied to Glioblastoma multiforme (GBM) data from The Cancer Genome Atlas (TCGA). Based on cellularity and nuclear size, four subtypes have been identified at the intermediate level. Subsequent multi-variate survival analysis indicates that the patient composition of one of the subtypes, with extremely low cellularity and small nucleus size, has a significantly higher hazard ratio. Further correlation of this subtype with the molecular data reveals enrichment of (i) STAT3 pathway and (ii) common regulators of PKC, TNF, AGT, and PDGF.

Original languageEnglish (US)
Title of host publicationProceedings - International Symposium on Biomedical Imaging
Pages1631-1634
Number of pages4
DOIs
StatePublished - 2012
Event2012 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012 - Barcelona, Spain
Duration: May 2 2012May 5 2012

Other

Other2012 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012
CountrySpain
CityBarcelona
Period5/2/125/5/12

Keywords

  • consensus clustering
  • Cox proportional-hazards model
  • molecular association
  • Tumor architecture

ASJC Scopus subject areas

  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging

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  • Cite this

    Han, J., Chang, H., Fontenay, G. V., Spellman, P. T., Borowsky, A. D., & Parvin, B. (2012). Molecular bases of morphometric composition in Glioblastoma multiforme. In Proceedings - International Symposium on Biomedical Imaging (pp. 1631-1634). [6235889] https://doi.org/10.1109/ISBI.2012.6235889