Hepatocellular carcinoma (HCC) (hereinafter referred to as liver cancer) is one of the most common malignant tumors. About 1 million people die from liver cancer every year in the world. The incidence of liver cancer in my country ranks first in the world, and the mortality rate of liver cancer is very high. It has become the second largest cancer killer in my country. The genes of hepatitis B virus can be integrated into the genome of liver cells, so it is called hepatitis B virus integration. At present, hepatitis B virus integration is believed to play an important role in the occurrence of liver cancer. Many researchers have carried out a lot of research in this regard, but due to the limitations of technology and the number of clinical samples, the further development of related research has been seriously hindered. On May 28, 2012, the results of the study on the integration mechanism of hepatitis B virus (HBV) jointly completed by the University of Hong Kong, the National University of Singapore, Shenzhen BGI, and the Asian Cancer Research Group (ACRG) (founded by Eli Lilly, Merck and Pfizer) were published online in the international authoritative journal Nature Genetics. This study constructed a high-precision and unbiased HBV integration map at the whole genome level for the first time, revealing the potential HBV integration mechanism, and providing very valuable resources for the early diagnosis, treatment and targeted drug development of liver cancer. In this study, researchers conducted whole genome sequencing and analysis on cancer tissue samples and adjacent tissue samples from 81 HBV-positive patients and 7 HBV-negative patients. The results showed that HBV integration is a common phenomenon in liver cancer, and the frequency of HBV integration in cancer tissue (86.4%) is significantly higher than that in adjacent tissue (30.7%). After combining transcriptome sequencing data analysis, the researchers discovered three new HBV integration sites (CCNE1, SENp5, ROCK1), and speculated that these genes may play a very important role in the occurrence of cancer. Based on the results of this study, the researchers speculated on the potential rules of HBV integration and its carcinogenic mechanism. They found that certain characteristics of HBV integration help the virus control the infected host genes, such as the bias of HBV integration sites and the increase in copy number variation (CNV) of HBV integration sites. These changes will affect the stability of chromosomes and cause changes in gene expression. In addition, the study also found that HBV integration is closely related to the clinical manifestations of patients. Patients with HBV integration will develop liver cancer earlier and have a lower cure rate. Therefore, intervention treatment of HBV integration may help prevent the deterioration of cancer and prolong the life of patients. Dr. Ken Sung, honorary associate professor at the University of Hong Kong and the National University of Singapore, who led the project, said: "This research result will provide new ideas for further in-depth research on the role of HBV integration in promoting the development of liver cancer and affecting clinical treatment. I hope that our next research work will further help improve the diagnosis and prevention of liver cancer." Zheng Hancheng, the project leader of BGI, said: "This is the first time to explore the molecular mechanism of HBV integration in liver cancer patients at the whole genome level. The data and research results we obtained will enable researchers to have a deeper understanding of the carcinogenicity of HBV. Considering the current less than ideal clinical treatment effect, we believe that full attention should be paid to vaccination prevention for high-risk groups, and clinical treatment strategies should be formulated from the perspective of HBV integrated intervention treatment, so as to effectively prevent the deterioration of cancer in patients and prolong their lives." "The molecular characteristics of tumors we have discovered in a larger group of cancer patients are of great scientific value in developing more targeted and effective drugs," said Dr. Christoph Reinhard, ACRG board member and senior director of oncology translational science at Eli Lilly and Company. "ACRG was established in the hope of accelerating research on the most common cancers in Asia through non-competitive collaboration, and this study also confirms the importance of solidarity and collaboration." |
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