NCI Cancer Bulletin for February 8, 2011 - National Cancer Institute: Protein May Help Predict Cancer Recurrence and Metastasis

Protein May Help Predict Cancer Recurrence and Metastasis

An altered form of a protein called CPE-delta N that is found in several cancer types may be used to predict cancer recurrence and metastasis with high sensitivity, reported an international team of researchers online February 1 in the Journal of Clinical Investigation.

The researchers, led by Drs. Terence Lee of the University of Hong Kong and Saravana Murthy of the National Institute of Child Health and Human Development, found that highly metastatic liver cancer cell lines had elevated levels of messenger RNA (mRNA) for CPE-delta N compared with liver cancer cells that were unlikely to spread. When the scientists blocked CPE-delta N expression in the metastatic cells using small interfering RNA (siRNA) technology, both cell growth and invasiveness were inhibited. Similar results were obtained with breast, colon, and head and neck cancer cell lines.

The researchers also found that CPE-delta N-expressing liver tumors implanted in mice grew as much as 16-times larger than control tumors containing siRNA that blocked CPE-delta N, and that the tumors without the siRNA block spread in the liver and to the lungs.

The researchers then evaluated whether CPE-delta N could be used as a biomarker to predict recurrence (including metastasis) in patients with hepatocellular carcinoma, a type of liver cancer. Using data from 99 patients, the researchers found that 75.8 percent of those whose disease did not return had CPE-delta N mRNA levels in their liver tumors that were no more than twice the level found in normal tissues. In contrast, 92.3 percent of patients whose tumors recurred had liver tumors with CPE-delta N mRNA levels greater than twice the level found in normal tissues. These findings translate to a sensitivity—the likelihood of the biomarker correctly predicting whether disease will recur—of 92.3 percent

A confirmatory study in 80 additional patients showed similar results. Importantly, explained the authors, CPE-delta N was able to predict risk of recurrence independent of tumor stage, a parameter that is commonly used to help predict risk of recurrence in the clinic.

The researchers then tested the predictive power of CPE-delta N in 14 patients with pheochromocytoma or paraganglioma, rare neuroendocrine tumors. They found that highly elevated copy numbers of CPE-delta N mRNA predicted recurrence with 100 percent accuracy in those patients.

“What’s unique about this paper is the fact that the marker works in two unrelated cancers,” said Dr. Stephen Hewitt, staff scientist in NCI’s Center for Cancer Research and a co-author on the paper. “Many biomarkers do not generalize into multiple tumor types.” If confirmed, CPE-delta N could be used to guide clinical care for some patients, such as sparing a patient whose tumor has already spread unnecessary surgery, he explained.


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NCI Cancer Bulletin for February 8, 2011 - National Cancer Institute