Cancer Research Lab

Altered patterns of microRNA expression in colon adenocarcinomas are associated with treatment response and prognosis, scientists report in the Journal of the American Medical Association for January 30. Dr. Aaron J. Schetter and Dr. Curtis C. Harris and colleagues identified one particular microRNA – miR-21 – that appears to actively promote tumor progression.

“Our findings show a systematic change in microRNA expression in colon tumors, suggesting a role for microRNAs in this process,” Drs. Schetter and Harris, at the National Cancer Institute in Bethesda, Maryland, said. “High miR-21 expression has also been found in 11 other cancer types, indicating that these findings may be relevant to other cancers.”

Using microarray analysis, the researchers compared microRNA expression in pairs of primary colon tumor and adjacent nontumorous tissues from 84 US patients. Five microRNAs with increased expression were associated with poor cancer survival.

Expression patterns for these 5 microRNAs accurately distinguished tumor from benign tissue in a validation cohort of 113 Hong Kong patients. Increased expression of miR-21 was associated with poor prognosis in both cohorts.

The authors found that in adenomas as well, miR-21 expression was elevated but to a lesser degree than in adenocarcinomas, and that more advanced malignancies expressed higher levels than less advanced tumors.

According to Dr. Schetter and Dr. Harris, this dose-response relationship indicates that “high miR-21 expression may be an early event in colon cancer initiation and progression.”

In multivariate analyses, high miR-21 expression in tumors was associated with poor survival independent of tumor staging in the US cohort (hazard ratio 2.7, p = .008) and in the Chinese cohort (HR 2.4, p = .002). Among 56 patients treated with fluorouracil-based chemotherapy, high miR-21 expression was associated with a worse response to therapy.

“We are currently planning in vitro and in vivo experiments to determine if miR-21 is the cause for the poor survival outcomes,” the researchers noted.

If that proves to be true, they added, “Work will also have to be done to find the most effective way of targeting miR-21, to determine how toxic these therapeutics may be, and how they can possibly be used along with current chemotherapy protocols to more effectively treat colon cancer.”