MicroRNA Biomarkers May Predict Colorectal Cancer Recurrence

Deborah Brauser

November 30, 2009

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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