How to treat liver cancer in the early stage? Analysis of targets for early treatment of liver cancer

Liver cancer is a common malignant tumor in the world, with a five-year survival rate of only 7%, ranking third among cancer-related deaths. Liver cancer has a very high incidence in Asia, especially in China, and is mainly caused by hepatitis B virus infection. There are more than 120 million chronic hepatitis B virus carriers in China, and 110,000 people die from liver cancer each year, accounting for almost half of the global liver cancer mortality rate.

Yesterday morning, Nature Cell Biology, a top international academic journal, published online a result of the Institute of Biochemistry and Cell Biology of the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. The research team led by Hui Lijian, a researcher at the institute, provided important targets for early diagnosis and prevention and treatment of liver cancer in the study of the molecular mechanism of early stage of liver cancer, which has the potential for application in prevention and treatment. This major discovery is ahead of the international level.

Since the molecular mechanisms of the early stages of liver cancer are not clear, early diagnosis of liver cancer is greatly limited, and patients diagnosed with liver cancer are usually already in the late stages of liver cancer. Except for a few patients who can undergo surgery, most patients with advanced liver cancer have almost no viable treatment options. In this case, finding molecular markers for the early stages of liver cancer and effective means of preventing and treating liver cancer has become an important direction in liver cancer treatment, and revealing the molecular mechanisms of the early stages of liver cancer has become the key.

According to researcher Hui Lijian, the research team he led used a gene-deficient mouse model to discover that in the early stages of liver cancer, c-Jun promoted tumorigenesis by inhibiting the expression of the c-Fos gene. Lower c-Fos levels reduce the level of acetyltransferase SIRT6, thereby increasing the expression of intracellular survivin, which ultimately leads to a decrease in tumor-initiating cell death, improves its survival, and promotes liver cancer. Through analysis of human liver cancer precancerous lesion tissue, they found that this molecular mechanism was also activated in the early stages of some human liver cancers, but did not change in late-stage liver cancers. More importantly, the researchers proved that increasing the SIRT6 content or inhibiting the activity of survivin in the early stages of liver cancer can inhibit the occurrence of liver cancer in mice.

This work is the first to isolate and identify a molecular mechanism that plays an important role in the early stages of liver cancer. In wild-type mice, targeted intervention of two important genes, SIRT6 and survivin, in this molecular mechanism can effectively inhibit the occurrence of liver cancer, providing potential target molecules for the prevention and treatment of liver cancer. This work was completed in collaboration with Erwin Wagner of the Spanish National Cancer Research Center, and the Zhongshan Hospital affiliated to the School of Medicine of Fudan University and other institutions participated in the collaborative research.

In May 2011, Hui Lijian's laboratory proved that somatic cells outside the liver can be induced to directly transform into liver cells, providing the possibility of inducing liver cells from the patient's own body cells for transplantation in the future. The results were published in NATURE. This revelation of the molecular mechanism of the early stage of liver cancer is another important contribution to the prevention and treatment of liver cancer.