title: Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse.
abstract: Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH) data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts) associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT). Resultant genes were classified based on gene ontology (GO), which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings.
authors.affiliation: Human Genetics Unit, Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait 13110, Kuwait. rabeah@hsc.edu.kw.
authors.forename: Rabeah A
authors.initials: RA
authors.lastname: Al-Temaimi
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore. csittz@nus.edu.sg.
authors.forename: Tuan Zea
authors.initials: TZ
authors.lastname: Tan
authors.affiliation: Kuwait Medical Genetics Center, Maternity Hospital, Kuwait 13001, Kuwait. mj_marafie@yahoo.com.
authors.forename: Makia J
authors.initials: MJ
authors.lastname: Marafie
authors.affiliation: Department of Biochemistry, National University of Singapore, Singapore 117599, Singapore. bchtjp@nus.edu.sg.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
authors.affiliation: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK. p.quirke@leeds.ac.uk.
authors.forename: Philip
authors.initials: P
authors.lastname: Quirke
authors.affiliation: Molecular Pathology Unit, Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait 13110, Kuwait. fahd@al-mulla.org.
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Mulla
mesh_terms: D000368:Aged; D000465:Algorithms; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D055028:Comparative Genomic Hybridization; D030541:Databases, Genetic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D015996:Survival Rate
keywords: colorectal cancer; copy number aberrations; disease free survival; gene expression; metastasis; microarray; stage II