Predictive gene signatures: molecular markers distinguishing colon adenomatous polyp and carcinoma

• Published in: PloS one 2014-11, Vol.9 (11), p.e113071-e113071
• Main Authors: Drew, Janice E, Farquharson, Andrew J, Mayer, Claus Dieter, Vase, Hollie F, Coates, Philip J, Steele, Robert J, Carey, Francis A
• Format: Article
• Language: English
• Subjects: Aberration; Adenomatous Polyps - diagnosis; Adenomatous Polyps - genetics; Analysis; Apoptosis; Architecture; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - metabolism; Biopsy; Cancer; Cancer genetics; Cancer screening; Carcinoma; CDX2 protein; Collagen (type I); Colon; Colonic Neoplasms - diagnosis; Colonic Neoplasms - genetics; Colonoscopy; Colorectal cancer; Customization; Development and progression; Diagnosis; Diagnosis, Differential; Discriminant analysis; Drug development; Engineering and Technology; Gene expression; Gene Expression Profiling; Genes; Genetic Markers; Genomes; Health aspects; Homeostasis; Hospitals; Humans; Immunohistochemistry; In Situ Hybridization; Markers; Medical prognosis; Medicine and Health Sciences; Metabolism; Mucin; Mucins; Multiplexing; Netrin-1; Nutrition; Pathology; Patients; Proliferating cell nuclear antigen; Real-Time Polymerase Chain Reaction; Research and Analysis Methods; Signatures; Stem cells; Transcription; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113071

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.