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Protein Marker Levels May Predict Liver Cancer Recurrence

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Every year, 39,230 American adults are diagnosed with primary liver cancer. The disease is the tenth most common cancer in the country, and it causes 27,170 deaths annually. One-year survival rates stand around 44 percent, but the number drops to 7 percent for five years. Death rates have increased steadily since 1980, making it more important than ever to find new ways to diagnose, treat and prevent recurrence.

A new discovery that links a particular protein to the reappearance of liver cancer in patients who were previously treated could provide doctors with a way to identify high-risk groups and administer targeted treatment regimens to increase chances of survival.

The Protein Link
In a study published in the journal Cancer Cell on May 19, researchers at the University of California San Diego School of Medicine and Sanford Burnham Prebys Medical Discovery Institute reported discovering a “strong link” between higher levels of a protein called p62 and the recurrence of liver cancer. The protein was also correlated with reduced rates of survival.

This discovery may prove to be particularly significant because, aside from chronic hepatitis infections, the actual causes of liver cancer are largely unknown. Early detection is key in treating cancer of all kinds, but liver cancer often doesn’t show symptoms until the later stages of the disease. Having a distinct marker that can be tested in patients who have already been treated for the cancer could help healthcare providers develop therapy regimens designed specifically around the action of p62.

What is p62?
The normal job of p62 is to tag damaged proteins within cells for breakdown by the body. By selectively marking these cellular components, p62 slows the cell aging process, promotes growth and allows stressed cells to survive. Under normal circumstances, this process benefits the body by supporting healthy cell function and turnover. However, in the case of cancer, it may allow damaged cells more time to mutate into malignant masses.

Uncovering the p62 Mechanism
Professor Michael Karin and his colleagues tested the involvement of p62 in liver cancer recurrence in two ways. First, they collected and studied 121 samples of non-cancerous liver tissue from patients who had previously undergone treatment to remove cancerous liver tumors. Each sample was rated based on the amount of p62 aggregates it contained. A total of 79 samples tested positive for the protein.

Karin and his group compared their results to data on survival rates from the patients’ records. Those with higher levels of p62 protein showed greater instances of recurrence and lower chances of living cancer-free in the long term. They also studied the data of 450 additional liver cancer patients with documented genomes and found similar outcomes in individuals with the p62 gene.

In the next phase of the experiment, Karin’s team used mice to test the action of p62 and found that, without the protein, liver tumors didn’t form at all. However, simply administering the protein seemed to be enough to spur on the development of cancer. All tests focused on hepatocellular carcinoma, the most common form of adult liver cancer.

Karin stated that “defining factors that allow liver cells to progress from pre-cancer to cancer, [allowed us] to find one – p62 – that we can also use to predict a liver cancer patient’s outcome following full removal of a previous liver tumor.” These findings could have significant implications for future treatment.

Applying the Science
Scientists will have to do a great deal of additional research and testing before Karin’s discoveries can be put into practice, but even a small understanding of the correlation existing between p62 and liver cancer could be helpful in predicting which patients are likely to experience a recurrence. By testing for levels of the protein, doctors could guide patients in optimal treatment decisions, potentially allowing them to live several years longer.

Levels of p62 have been found to be elevated in other types of cancer and in precancerous liver diseases. Now that a known link has been found between the protein and liver cancer, research into these other conditions may uncover further information that could be used to help thousands more patients by developing treatments to specifically target the actions of p62.

More research into p62 and how its role in cellular growth could be addressed to create these new procedures could be a big step forward in the treatment of liver cancer. Lowering death rates and improving survival outcomes would provide a ray of hope for the thousands of Americans living with this disease.

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