The researchers found higher levels of p62 is linked to higher chance of liver cancer recurrence and reduced patient survival.
Prof. Michael Karin, of the University of California-San Diego School of Medicine, and colleagues describe their findings about the protein - called p62 - in the journal Cancer Cell.
They discovered when the liver tissue that remains after tumors have been removed tests positive for high levels of p62, the cancer is more likely to recur and patient survival is reduced.
They also found that without the protein, liver tumors did not form in mouse models of the disease.
Prof. Karin and colleagues suggest p62 could be a biomarker for liver cancer recurrence and a target for treatment.
New ways of detecting and preventing liver cancer are badly needed. The disease has a low survival rate because symptoms often do not appear until the later stages.
According the American Cancer Society, only 17 percent of patients wilth all types of cancer of the liver and bile duct survive 5 years cancer-free after treatment.
The normal role of p62 is to collect the cell's trash and deliver proteins marked for destruction to the cell's recycling center.
The protein also acts as a communication hub for the cell. It does this by binding to proteins that control important cell functions such as growth and survival.
Protein promotes cancer by helping stressed cells survive
The team investigated p62 because high levels of the protein have been found in many different cancers, including liver cancer, and in pre-cancerous liver diseases.
For the new study, the researchers tested non-cancerous liver tissue collected from patients who had undergone treatment to completely remove their liver tumors.
They confined their investigation to hepatocellular carcinoma, the most common form of adult liver cancer.
The researchers gave each sample a grade from 0-3, depending on the average number of protein aggregates that tested positive for p62. Of the 121 samples they tested, 79 were positive for p62.
The team then correlated the p62 grade of each tissue sample against the medical records of the patients the samples came from, noting the number of years that each patient had lived without a recurrence of their cancer.
The analysis showed patients with high-grade p62 samples were more likely to have a recurrence of their cancer and less likely to survive cancer-free than patients whose samples had low or zero p62 scores.
The researchers found the same result in another 450 liver cancer patients whose genome data and clinical records they retrieved from national research databases.
In the next phase of the study, the team used mice to show that p62 promotes cancer by activating other proteins and genes that help stressed cells survive. The longer stressed liver cells live, the more mutations they accumulate, raising the risk that tumors will develop.
The researchers found that p62 was necessary and sufficient for liver cancer to develop in several mouse models of the disease: liver tumors did not form if the protein was absent.
"By defining factors that allow liver cells to progress from pre-cancer to cancer, we were able 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."
Prof. Michael Karin
The team believes that small molecules that disrupt p62 could be a starting point for new drugs that prevent chronic liver disease from developing into liver cancer.
However, several years of further tests lie ahead before doctors will be able to use p62 to make treatment decisions.