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.
Dr Aaron Schetter and colleagues from Texas, USA identified microRNA expression patterns associated with colon adenocarcinomas, prognosis, or therapeutic outcome.
|miR-21 was expressed at high levels in colonic carcinoma cells|
|Journal of the American Medical Association|
The team performed MicroRNA microarray expression profiling of tumors and paired nontumorous tissues on a USA test cohort.
The research team evaluated 84 patients with incident colon adenocarcinoma, recruited between 1993 and 2002.
The team evaluated associations with tumor status, tumor node metastases (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.
The team used quantitative reverse transcription polymerase chain reaction assays.
The final date of follow-up was 2005 for the Maryland cohort, and 2004 for the Hong Kong cohort.
The researchers evaluated microRNAs that were differentially expressed in tumors, and microRNA expression patterns associated with survival using cancer-specific death as the end point.
The team found that 37 microRNAs were differentially expressed in tumors from the test cohort.
The researchers selected for validation miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort.
Higher miR-21 expression was present in adenomas, and in tumors with more advanced TNM staging.
In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells.
The team found the 5-year cancer-specific survival rate was 58% for the Maryland cohort, and was 50% for the Hong Kong cohort.
High miR-21 expression was associated with poor survival in both the training, and validation cohorts, independent of clinical covariates, including TNM staging.
The research team observed that a high miR-21 was associated with a poor therapeutic outcome.
Dr Schetter's team concluded, "Expression patterns of microRNAs are systematically altered in colon adenocarcinomas."
"High miR-21 expression is associated with poor survival and poor therapeutic outcome."