MAY 13, 2015 06:00 AM PDT

Predictive Gene Signatures: Molecular Markers Distinguishing Colon Adenomatous Polyp and Carcinoma

Speakers
  • Senior Research Fellow, MSc Human Nutrition, Course Co-ordinator for Molecular Nutrition, University of Aberdeen, Rowett Institute of Nutrition and Health, Metabolic Health Group
    Biography
      Dr. Janice Drew is a Senior Research Fellow in the Rowett Institute of Nutrition and Health within the College of Life Sciences and Medicine at the University of Aberdeen. She received a BSc Hons (First Class) degree from the University of Strathclyde (Glasgow, UK) in 1991 conducting her honours project on plant bioactives produced from genetically transformed root cultures. She pursued graduate work at the University of Durham (UK) and received her Ph.D. in molecular biology in 1994. Subsequently, Dr. Drew trained as a postdoctoral fellow in molecular neuroendocrinology, investigating G protein coupled receptor signalling in circadian rhythms and appetite and energy balance at the Rowett Research Institute (Aberdeen, UK) supported by a Strategic Alliance with Servier (France).

      Dr. Drew has developed research programmes in cross therapeutic areas investigating diet:gene interactions and links with gut and metabolic health. Her work utilises systems approaches incorporating genomic, proteomic, biochemical and physiological analyses to identify molecular mechanisms linking diet and lifestyle factors to gut and metabolic health. Her research in this area has investigated regulatory pathways of genes involved in key processes such as, proliferation, differentiation and apoptosis, inflammation and signalling systems such as adipokine and endocannabinoid, using in vitro cell and ex vivo human colon explant cultures, in vivo models, tissue and organ systems, blood profiling and human intervention studies. Her current focus is directed to study of the regulation and modulation of the sirtuin/NAD system as a nutrient and stress sensor and associations with metabolic health status, cancer and longevity.

    Abstract:

    Cancers exhibit abnormal molecular signatures associated with disease initiation and progression. Molecular signatures could improve cancer screening, detection, drug development and selection of appropriate therapeutic interventions for individual patients. Typically only very small amounts of tissue are available from patients for analysis and biopsy samples exhibit broad heterogeneity that cannot be captured using a single marker. This presentation details application of in-house custom designed GenomeLab System multiplex gene expression assays. Details of design, tissue optimisation, total RNA quality and analytical and clinical validation will be discussed. Application to assess predictive gene signatures of normal, adenomatous polyp and carcinoma colon tissue using archived tissue bank material and an in-house custom designed human cell marker multiplex, the hCellMarkerPlex will be presented. The hCellMarkerPlex incorporates twenty-one gene markers: epithelial (EZR, KRT18, NOX1, SLC9A2), proliferation (PCNA, CCND1, MS4A12), differentiation (B4GANLT2, CDX1, CDX2), apoptotic (CASP3, NOX1, NTN1), fibroblast (FSP1, COL1A1), structural (ACTG2, CNN1, DES), gene transcription (HDAC1), stem cell (LGR5), endothelial (VWF) and mucin production (MUC2). Gene signatures distinguished normal, adenomatous polyp and carcinoma. Individual gene targets significantly contributing to molecular tissue types, classifier genes, were further characterised using real-time PCR, in-situ hybridisation and immunohistochemistry revealing aberrant epithelial expression of MS4A12, LGR5 CDX2, NOX1 and SLC9A2 prior to development of carcinoma. Identified gene signatures identify aberrant epithelial expression of genes prior to cancer development using in-house custom designed gene expression multiplex assays. This approach may be used to assist in objective classification of disease initiation, staging, progression and therapeutic responses using tissue biopsy material.


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