Tumor's protein level predicts if cancer will spread

Researchers have found a way to detect if cancer has spread or if it will recur by testing the tumor for a certain protein, said a study on Tuesday in the journal Clinical Investigation.

The discovery could provide a more accurate indication of likely survival than the current method of grading cancer stages from one to four, researchers said.

If the test can be developed for wider use, which could still be years away, it may help doctors decide when to aggressively treat tumors to try to prevent them from metastasizing, often fatally, to other parts of the body.

"This biomarker may be useful for many types of cancers," said lead study author Y. Peng Loh of the US National Institute of Child Health and Human Development's (NICHD) Section on Cellular Neurobiology.

"It is very important to know when a cancer is likely to spread," she said. "Currently there are no accurate biomarkers that can achieve such predictions and prognosis is determined by staging of the cancer."

The new variant of a protein, carboxypeptidase E (CPE), usually involved with processing of hormones, such as insulin, was discovered by scientists at the US National Institutes of Health and the University of Hong Kong.

The protein, CPE-delta N, was found to be present at high levels in metastatic tumor cells in numerous types of cancer, including liver, breast, colon, adrenal and head and neck cancers.

The eight-year study focused on 99 patients with stage one to four liver cancer, and tested tumor cells and surrounding tissue for levels of CPE delta-N by measuring RNA (ribonucleic acid) which helps the body make the protein.

When the level of CPE delta-N RNA in tumors was more than double that in the surrounding tissue, "the cancer was highly likely to return or to metastasize within two years," the study said.

"At or below this threshold level, the cancer was much less likely to recur," it said.

According to that method, researchers predicted that cancer had metastasized or would recur in more than 90 percent of cases, and they were correct 76 percent of the time when they predicted the tumors would not come back.

In some cases, they found that the protein indicated cancer would return in stage two patients who normally would have been presumed cancer-free and would not have received further care after the tumor was excised.

"So CPE delta N is a better indicator of the seriousness of the disease than current staging techniques," said Loh.

The scientists also extracted cells from other types of tumors and analyzed them for the protein, extending the study to a total of 180 patients.

Biomarker research has been plagued by announcements of promising indicators of disease that upon further study have fallen flat.

But Loh said the research team followed strict guidelines for publishing their study and were confident that they established a "basis on which to go further."

The National Cancer Institute's Stephen Hewitt, a scientist who contributed to the research, said the RNA method provided a better way to diagnose cancer.

"This study is nice because we were able to beat the current standard of care of stage and grade," he said.

However, he cautioned that the research will take time to develop into a test that is available to the general public.

"We are at a stage where we have a discovery - and a very good result - but it is time to validate this and other cohorts and expand these findings, including to other tumor types," said Hewitt.

"The nature of biomarker development is very much like the nature of drug development, it takes time," he said.

"And sometimes you actually have to wait longer than with drug development because you are waiting for the patient's outcome to be determined," he said.

The lead authors of the study were Loh and Ronnie Poon from the University of Hong Kong, and funding came in part from the NICHD, National Cancer Institute, University of Hong Kong and the Canadian government.



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