title: An evaluation and replication of miRNAs with disease stage and colorectal cancer-specific mortality.
abstract: MicroRNAs (miRNAs) have been implicated in colorectal cancer (CRC) development and associated with prognostic indicators such as disease stage and survival. Prognostic associations are often based on few individuals and imprecise. In this study, we utilize population-based data from 1,141 CRC cases to replicate previously reported associations between 121 miRNAs and disease stage and survival. The Agilent Human miRNA Microarray V19.0 was used to generate miRNA data following a stringent quality control protocol. Assessment of survival was done using Cox Proportional Hazard models adjusting for age, disease stage and tumor molecular phenotype. Five miRNAs were associated with more advanced disease stage; hsa-miR-145-5p and hsa-miR-31-5p showed increased expression with more advanced tumor stage, while hsa-miR-200b-3p, hsa-miR-215 and hsa-miR-451a had decreased expression with more advanced tumors. Thirteen miRNAs were associated with CRC mortality among individuals diagnosed with colon cancer while 14 were associated with CRC mortality after a diagnosis with rectal cancer. Strongest associations were observed for those miRNAs that were expressed in a small subset of tumors. Most notable associations were for hsa-miR-145-3p [hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.54, 5.61], and hsa-miR-9-3p (HR 10.28, 95% CI 1.31, 80.84) with colon cancer and hsa-miR-335-5p (HR 0.17, 95% CI 0.05, 0.54) for rectal cancer. hsa-miR-374a-5p, hsa-miR-570-3p and hsa-miR-18a-5p significantly reduced the hazard of dying for all cases, regardless of tumor site. Our findings illustrate the need for a large sample to evaluate the association of miRNAs with survival and disease stage in order to determine associations by tumor site.
authors.affiliation: Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Herrick
authors.affiliation: Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT.
authors.forename: Lila E
authors.initials: LE
authors.lastname: Mullany
authors.affiliation: Centre for Molecular Pathology, The Institute of Cancer Research and The Royal Marsden NHS Trust, Sutton Surrey SM2 5NG, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Valeri
authors.affiliation: Department of Mathematics and Statistics, Utah State University, 3900 Old Main Hill, Logan, UT.
authors.forename: John
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Division of Research, Kaiser Permanente, Oakland, CA.
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.affiliation: Department of Pathology, University of Utah School, Salt Lake City, UT.
authors.forename: Wade
authors.initials: W
authors.lastname: Samowitz
authors.affiliation: Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data; D011159:Population Surveillance / Q000379:methods; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: C541010:MIRN145 microRNA, human; C556347:MIRN335 microRNA, human; C587995:MIRN374 microRNA 374, human; C582115:MIRN570 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs
keywords: colorectal cancer; miRNA; survival