Concentration of Tumor Protein Predicts Metastatic Cancer

Molecular techniques have revealed that high levels of a particular protein in tumor cells are a reliable indicator that the cancer will metastasize.

By measuring a protein biomarker in a tumor and comparing the levels in surrounding tissue, it is possible to predict whether the cancer will spread to other organs within two years.

Scientists collaborating with the University of Hong Kong, (Hong Kong SAR, China) studied the protein carboxypeptidase E (CPE) in a form known as CPE-delta N. CPE-delta N, a variant of CPE, and is present in high amounts in tumors that have spread, and only in small amounts in the surrounding tissues. Ordinarily, CPE is involved in processing insulin and other hormones. They tested for CPE-delta N indirectly, by measuring levels of ribonucleic acid (RNA). RNA works with the information in a gene to make a particular protein as in this case, CPE-delta N. In an analysis of tissue from 99 patients with liver cancer, they compared the amount of CPE-delta N RNA from the patients' tumors with the RNA levels in surrounding tissue. The status of the patients' morbidity was tracked for up to eight years.

The scientists found that when the level of CPE delta-N RNA in tumors was more than twice that in the surrounding tissue, the cancer was highly likely to return or to metastasize within two years. At or below this threshold level, the cancer was much less likely to recur. Using this threshold measure, the investigators accurately predicted metastasis or recurrence in more than 90% of the cases. Conversely, their predictions that tumors would not return in the two-year period were accurate 76% of the time. They also measured CPE-delta N RNA levels from stored tumor tissue originally removed from 14 patients with pheochromocytoma, a rare tumor of the adrenal glands, and paraganglioma, a rare tumor primarily occurring in the adrenals but sometimes in other parts of the body. The number of copies ranged from 150,000 to 15 million per 200 micrograms of tissue. In all of the cases where cancer was found to have recurred or metastasized, CPE-delta N RNA levels were greater than one million. The researchers found no metastasis or recurrence in cases in which tumors had less than 250,000 copies.

In addition, the scientists examined cells from liver, breast, colon, and head and neck, tumors and found that those known to spread most aggressively had the highest levels of CPE-delta N RNA. Y. Peng Loh, PhD, a senior author of the study, explained that the method used in the study might someday be used to treat cancers in human beings. Currently, there are no means to deliver the antisense RNA to tumor cells. A potential approach might involve modifying a virus to carry the antisense RNA into cells. The study was published on February 1, 2011 in the Journal of Clinical Investigation.

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