title: Recurrence of early stage colon cancer predicted by expression pattern of circulating microRNAs.
abstract: Systemic treatment of patients with early-stage cancers attempts to eradicate occult metastatic disease to prevent recurrence and increased morbidity. However, prediction of recurrence from an analysis of the primary tumor is limited because disseminated cancer cells only represent a small subset of the primary lesion. Here we analyze the expression of circulating microRNAs (miRs) in serum obtained pre-surgically from patients with early stage colorectal cancers. Groups of five patients with and without disease recurrence were used to identify an informative panel of circulating miRs using quantitative PCR of genome-wide miR expression as well as a set of published candidate miRs. A panel of six informative miRs (miR-15a, mir-103, miR-148a, miR-320a, miR-451, miR-596) was derived from this analysis and evaluated in a separate validation set of thirty patients. Hierarchical clustering of the expression levels of these six circulating miRs and Kaplan-Meier analysis showed that the risk of disease recurrence of early stage colon cancer can be predicted by this panel of miRs that are measurable in the circulation at the time of diagnosis (P = 0.0026; Hazard Ratio 5.4; 95% CI of 1.9 to 15).
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, District of Columbia, United States of America.
authors.forename: Narayan
authors.initials: N
authors.lastname: Shivapurkar
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, District of Columbia, United States of America.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiner
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, District of Columbia, United States of America.
authors.forename: John L
authors.initials: JL
authors.lastname: Marshall
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, District of Columbia, United States of America.
authors.forename: Subha
authors.initials: S
authors.lastname: Madhavan
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, District of Columbia, United States of America.
authors.forename: Anne
authors.initials: A
authors.lastname: Deslattes Mays
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, District of Columbia, United States of America ; Indivumed GmbH, Hamburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Juhl
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, District of Columbia, United States of America.
authors.forename: Anton
authors.initials: A
authors.lastname: Wellstein
mesh_terms: D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D012008:Recurrence; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D035683:MicroRNAs