1. Home>
2. Specialties>
3. Gastroenterology>
4. Summary and Comment

MicroRNAs and Colon Cancer

High microRNA expression was associated with poor prognoses among 197 patients with colon cancer.

MicroRNAs regulate cell processes, including proliferation and apoptosis, and these noncoding RNA molecules show altered expression in many tumors that arise in pancreatic cancer, lung cancer, and chronic lymphocytic leukemia. A causal role for microRNA overexpression in carcinogenesis is less certain, but, if such an association is confirmed, it might provide an opportunity for chemotherapy via antisense nucleotides that inhibit microRNA function. Further, if microRNAs demonstrate prognostic value, they could serve as biomarkers for selection of chemotherapeutic agents.

Investigators examined the relation between microRNA expression and colon cancer prognoses in paired tumor and nontumor tissue samples from a test cohort of 84 U.S. patients with colon adenocarcinomas. They constructed a model that predicted prognoses based on levels of expression of certain microRNAs, and they tested the model in a validation cohort of 113 Chinese adenocarcinoma patients.

Twenty-six microRNAs were expressed at higher levels in tumor versus nontumor tissue. The microRNA miR-21, overexpressed by 1.8-fold in tumor tissue, was the most abundant. In the test cohort, five microRNAs were associated with poor 5-year survival (P<0.05), including miR-21 (hazard ratio, 2.5; 95% CI, 1.2–5.0). In the validation cohort, high miR-21 expression (HR, 2.4; 95% CI, 1.4–3.9) and high tumor-node-metastasis staging (HR, 4.7; 95% CI, 2.4–9.5) were associated with poor 5-year survival. Several microRNAs, including miR-21, were overexpressed in tissue-bank adenoma samples, but microarray analysis showed that their expression levels were higher in tumors and increased with advancing cancer stage. Tumor immunostaining showed that miR-21 in colonic epithelial cells was expressed at higher levels in tumor tissue than in nontumor tissue. Although adjuvant chemotherapy provided a survival benefit for patients overall, multivariate analysis showed that high miR-21 expression was associated with poor prognoses among chemotherapy-treated patients with stage II or III colon cancers.

Comment: Although gastroenterologists’ major focus is preventing colorectal cancer, we typically maintain familiarity with biologic factors that affect prognosis and treatment of the disease. MicroRNA expression in colon cancer is an emerging area of interest, as it likely will highlight the need for more-aggressive chemotherapy and might provide the ability to generate specific therapeutic antimicroRNA molecules if, indeed, microRNA overexpression is shown to cause cancer.

— Douglas K. Rex, MD

Published in Journal Watch Gastroenterology February 22, 2008

Citation(s):

Schetter AJ et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 2008 Jan 30; 299:425.

• Original article (Subscription may be required)
• Medline abstract (Free)