Study Shows Potential for microRNAs to Determine Risk of Recurrence in Colorectal Cancer

The article, entitled "Tumor microRNA-29a expression and the risk of recurrence in stage II colon cancer," can be accessed at http://www.spandidos-publications.com/confirmCorrespondingEmail?transactionId=3078312e33363161366462343330636264703430 .

The study compared the microRNA (miRNA) profiles in the primary tumor of patients with recurrent and non-recurrent colorectal cancer. The study included 110 patients, 51 (46%) with stage I and 59 (54%) with stage II disease, who underwent curative colectomies without adjuvant therapy and for whom reliable miRNA expression data was available. RNA was extracted from formalin-fixed paraffin-embedded tumor samples. Initial profiling, using microarrays, was done to identify potential biomarkers of recurrence. The miRNA expression was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). The findings compared the miRNA profiles between patients who had a recurrence within 36 months of surgery (bad prognosis group, n=23 or 21%) and those who did not (good prognosis group, n=87 or 79%) in the entire group and within each stage.

In stage II patients, one miRNA, miR-29a, showed a clear differential expression between the good and bad prognosis groups (p=0.028). High expression of miR-29a was associated with a longer disease-free survival on both univariate and multivariate analyses. Using miR-29a, the positive predictive value for non-recurrence was 94% (2 recurrences among 31 patients). The differential expression of miR-29a was verified by qRT-PCR, showing a similar association of this miRNA with disease-free survival. The results showed that none of the 903 miRNAs tested showed differential expression between stage I patients with good and bad prognosis.

Commenting on these data, study collaborator, Baruch Brenner, M.D., Institute of Oncology, Davidoff Center, Rabin Medical Center, Beilinson Hospital and Sackler Faculty of Medicine, Tel Aviv University, both in Israel, noted, "The risk of recurrence following successful complete resection is high in stage II and III disease. Consequently, most of these patients will receive additional treatment including postoperative (adjuvant) chemotherapy and preoperative (neoadjuvant) or postoperative (adjuvant) chemo-radiotherapy. However, the majority of patients receiving neoadjuvant and/or adjuvant therapy, which are associated with significant morbidity and even long-term sequelae and mortality, do not need it."

Dr. Brenner continued, "The current study suggests a potential prognostic role of miR-29a in patients with resected stage II colon cancer. Patients who did not experience a recurrence within three years from the resection of their primary tumor had significantly higher expression levels of this miRNA compared with patients who did have a recurrence within the same time. To further support the prognostic role of miR-29a, high expression levels of this miRNA correlated not only with the risk of recurrence, but also with the duration of disease-free survival."

"Current methods for stratifying patients with colorectal cancer by their prognosis are still mainly based on the extent of the local tumor spread and do little to distinguish between patients who do and those who do not need additional treatment," stated Kenneth A. Berlin, President and Chief Executive Officer of Rosetta Genomics. "Colorectal cancer is one of the most common cancers. Globally, more than 500,000 people die of this disease each year, making it the third most common cancer death worldwide. Data from this study demonstrate that miR-29a has the potential to serve as a biomarker of the risk of recurrence in stage II colon cancer, a finding that may have important implications for patient care. Informed decision-making using a test with a high positive predictive value may spare patients unnecessary and sometimes toxic post-surgery treatment, and may identify which patients to treat more aggressively."