November 30, 2009 (Orlando, Florida) — In addition to distinguishing between tumor tissue and healthy tissue from patients who have colorectal cancer (CRC), microRNAs can potentially predict CRC recurrence in stage II patients, according to a new study presented here at the Association for Molecular Pathology (AMP) 2009 Annual Meeting.
|Dr. Elizabeth Mambo|
Moreover, this predictive ability was independent of both microsatellite instability (MSI) and KRAS status.
"Stage II [CRC] is not a simple disease," said investigational team member Elizabeth Mambo, PhD, senior scientist at Asuragen, Inc, in Austin, Texas, during her podium presentation. "It's a heterogeneous disease for which we need to understand the pathways that are involved."
She reported that up to 40% of stage II CRC patients will experience recurrence — usually within 2 to 3 years. "Yet the current state of disease management administers adjuvant therapy only to patients diagnosed with later stages of the disease."
Therefore, the objective of this study was to examine the ability of microRNAs to distinguish high risk from low risk for recurrence in stage II CRC tissue. The investigators also compared microRNA expression signatures associated with early-stage CRC tumors and those associated with normal adjacent tissues (NAT), according to the presentation.
Potentially Diagnostic and Prognostic
Dr. Mambo and colleagues evaluated 20 matched pairs of formalin-fixed, paraffin-embedded human colorectal samples and NAT, concentrating on stage IIA tumors because they "represent 85% of all stage II patients," explained Dr. Mambo.
For verification studies, another 46 stage II tumors (22 from recurrent patients, 24 from nonrecurrent patients) were examined.
The investigators used custom-manufactured DNA microarrays and quantitative reverse-transcription polymerase chain reaction for the evaluations.
Results showed that "microRNA-21 and microRNA-31 were significantly upregulated [t test P value, 6.1 × 10–7 and 3.8 × 10–4, respectively] in CRC, compared with NAT," explained Dr. Mambo. "In addition, 4 microRNAs were found that were upregulated and several others were downregulated in cancers."
When the investigators examined microRNAs associated with CRC recurrence, they found that most were downregulated in the stage II patients that had experienced recurrence, as opposed to those with nonrecurrence.
Finally, the validation studies showed 11 microRNAs that were potentially prognostic for recurrence of CRC tumors.
"Our research data provides support for the clinical utility of microRNAs, both as potentially diagnostic and prognostic biomarkers for [CRC]," said Dr. Mambo.
"We found that microRNA expression patterns can distinguish colorectal tumor tissues from matched [NAT], can predict [CRC] recurrence in node-negative early-stage patients, and may offer better prognostic markers than those that are currently used, such as MSI and KRAS," summarized Dr. Mambo.
"Although the sample was small, we believe that we have identified a microRNA signature that should be very useful and is worthy of further investigation," she explained.
Promising but Preliminary
"I think this study is interesting but very preliminary," said session moderator Loren Joseph, MD, from the University of Chicago School of Medicine and cochair of the AMP Solid Tumors subgroup. He was not involved with this study.
"A question was raised after the presentation about how the correlation of KRAS and MSI was handled; that could probably stand some revisiting. But as a topic, trying to identify which stage IIA colon cancers need treatment — that's extremely important, and this looks like a promising step in that direction," concluded Dr. Joseph.
This study was funded by Asuragen, who also employs Dr. Mambo. Dr. Joseph has disclosed no relevant financial relationships.
Association for Molecular Pathology (AMP) 2009 Annual Meeting: Abstract ST30. Presented November 20, 2009.
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Cite this: MicroRNA Biomarkers May Predict Colorectal Cancer Recurrence - Medscape - Nov 30, 2009.