INVESTIGATIONS of p62 have highlighted the protein as a key factor in cancer recurrence and has been associated with reduced rates of survival in liver cancer patients, according to a recent study carried out by Prof Michael Karin, Department of Pharmacology, San Diego School of Medicine, Los Angeles, California, USA, and colleagues.
The protein has been repeatedly detected in various forms of cancer, including liver cancer and pre-cancerous liver diseases, prompting the team to investigate it as a trigger for hepatocellular carcinoma (HCC), the most common form of liver cancer. Tissue samples were collected from patients following tumour removal, consisting of 121 samples which were then graded from 0–3 based on the average number of protein aggregates that tested positive for p62. Of the samples, 79 tested positive for p62; the data were then compared against the patients’ medical records to compare p62 to rates of recurrence and survival. Higher levels of p62 were found to be linked to a higher chance of hepatic cancer recurrence and reduced patient survival than low or zero p62 scores. The same outcome was achieved in another assessment, comprising 450 patients with liver cancer, in which the team analysed genome data and clinical records obtained from national research databases.
In a subsequent phase, which tested mice, the researchers observed that p62 causes cancer to develop by activating other proteins or genes that maintain the survival of stressed HCC-initiating cells. Mutations accumulate as these cells survive, increasing the risk of tumours. It was established that liver tumours would only develop in the mouse models if the protein was present. The team suggests that p62 is therefore necessary for liver cancer to develop, which indicates that the protein could be a biomarker for the disease, allowing clinicians to predict liver cancer and target treatment. Prof Karin summarised the findings: “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 tumour.” Low survival rates from liver cancer mean new research concerning liver cancer such as this is imperative, and the team believes that further studies into the inhibition p62’s promotion of cancer growth could be a crucial starting point for new treatments.