CONTEXT: MicroRNAs have potential as diagnostic biomarkers and therapeutic 
targets in cancer. No study has evaluated the association between microRNA 
expression patterns and colon cancer prognosis or therapeutic outcome.
OBJECTIVE: To identify microRNA expression patterns associated with colon 
adenocarcinomas, prognosis, or therapeutic outcome.
DESIGN, SETTING, AND PATIENTS: MicroRNA microarray expression profiling of 
tumors and paired nontumorous tissues was performed on a US test cohort of 84 
patients with incident colon adenocarcinoma, recruited between 1993 and 2002. We 
evaluated associations with tumor status, TNM staging, survival prognosis, and 
response to adjuvant chemotherapy. Associations were validated in a second, 
independent Chinese cohort of 113 patients recruited between 1991 and 2000, 
using quantitative reverse transcription polymerase chain reaction assays. The 
final date of follow-up was December 31, 2005, for the Maryland cohort and 
August 16, 2004, for the Hong Kong cohort.
MAIN OUTCOME MEASURES: MicroRNAs that were differentially expressed in tumors 
and microRNA expression patterns associated with survival using cancer-specific 
death as the end point. RESULTS Thirty-seven microRNAs were differentially 
expressed in tumors from the test cohort. Selected for validation were miR-20a, 
miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from 
the validation cohort (P < .001). Higher miR-21 expression was present in 
adenomas (P = .006) and in tumors with more advanced TNM staging (P < .001). In 
situ hybridization demonstrated miR-21 to be expressed at high levels in colonic 
carcinoma cells. The 5-year cancer-specific survival rate was 57.5% for the 
Maryland cohort and was 49.5% for the Hong Kong cohort. High miR-21 expression 
was associated with poor survival in both the training (hazard ratio, 2.5; 95% 
confidence interval, 1.2-5.2) and validation cohorts (hazard ratio, 2.4; 95% 
confidence interval, 1.4-3.9), independent of clinical covariates, including TNM 
staging, and was associated with a poor therapeutic outcome.
CONCLUSIONS: Expression patterns of microRNAs are systematically altered in 
colon adenocarcinomas. High miR-21 expression is associated with poor survival 
and poor therapeutic outcome.