Predictive gene signatures

molecular markers distinguishing colon adenomatous polyp and carcinoma

Janice E. Drew, Andrew J. Farquharson, Claus Dieter Mayer, Hollie F. Vase, Philip J. Coates, Robert J. Steele, Francis A. Carey

Research output: Contribution to journalArticle

16 Citations (Scopus)
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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 drug therapies 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 report details application of an in-house custom designed GenomeLab System multiplex gene expression assay, the hCellMarkerPlex, to assess predictive gene signatures of normal, adenomatous polyp and carcinoma colon tissue using archived tissue bank material. 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 biopsy material.
Original languageEnglish
Article number0113071
JournalPloS ONE
Volume9
Issue number11
DOIs
Publication statusPublished - 25 Nov 2014

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Adenomatous Polyps
carcinoma
colon
Colon
Genes
Carcinoma
genetic markers
genes
Tissue
gene expression
neoplasms
Biopsy
biopsy
Gene Expression
Gene expression
Assays
Tissue Banks
mucins
assays
Drug therapy

Cite this

Drew, J. E., Farquharson, A. J., Mayer, C. D., Vase, H. F., Coates, P. J., Steele, R. J., & Carey, F. A. (2014). Predictive gene signatures: molecular markers distinguishing colon adenomatous polyp and carcinoma. PloS ONE, 9(11), [0113071]. https://doi.org/10.1371/journal.pone.0113071

Predictive gene signatures : molecular markers distinguishing colon adenomatous polyp and carcinoma. / Drew, Janice E.; Farquharson, Andrew J.; Mayer, Claus Dieter; Vase, Hollie F.; Coates, Philip J.; Steele, Robert J.; Carey, Francis A. .

In: PloS ONE, Vol. 9, No. 11, 0113071, 25.11.2014.

Research output: Contribution to journalArticle

Drew, JE, Farquharson, AJ, Mayer, CD, Vase, HF, Coates, PJ, Steele, RJ & Carey, FA 2014, 'Predictive gene signatures: molecular markers distinguishing colon adenomatous polyp and carcinoma', PloS ONE, vol. 9, no. 11, 0113071. https://doi.org/10.1371/journal.pone.0113071
Drew, Janice E. ; Farquharson, Andrew J. ; Mayer, Claus Dieter ; Vase, Hollie F. ; Coates, Philip J. ; Steele, Robert J. ; Carey, Francis A. . / Predictive gene signatures : molecular markers distinguishing colon adenomatous polyp and carcinoma. In: PloS ONE. 2014 ; Vol. 9, No. 11.
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