Nature Subsidiary: Blood test for liver cancer, Chinese scholars teamed up to bring early diagnosis of heavyweight tools

Release date: 2017-10-13

Liver cancer is a terminal illness. It is not only difficult to treat, but when the patient is diagnosed, the condition often progresses to the advanced stage, further increasing the difficulty of treatment. If there is an easy-to-use method for early diagnosis of liver cancer, early treatment can be achieved to improve the survival rate of patients with liver cancer.

Professor Xu Ruihua (left) and Professor Zhang Kang (right)

This tool may have been born! Professor Xu Ruihua from the Cancer Center of Sun Yat-sen University and Professor Zhang Kang of the University of California San Diego School of Medicine jointly developed an innovative liver cancer diagnosis technology. By analyzing the circulating tumor DNA (ctDNA) in the blood, they can perform early diagnosis and detection of liver cancer, or a prognostic therapy. The study, which is expected to benefit patients fundamentally, was published online today in Nature, a supplement to Nature Materials.

Hepatocellular carcinoma is the most common type of primary liver cancer in adults and one of the leading causes of cancer death worldwide. Like many cancers, early detection can significantly improve patient outcomes and survival rates. On the one hand, cancer sickness has not spread to the whole body at an early stage; on the other hand, the effect of local treatment is often better than systemic treatment. But unfortunately, early detection is not easy for hepatocellular carcinoma - currently, detection of this cancer relies mainly on imaging and blood testing of the non-specific tumor marker alpha-fetoprotein (AFP). When its level rises to the point where it can be accurately detected, cancer has already made significant progress.

Professor Zhang Kang, part of the laboratory (Source: Sun Yat-Sen University)

“In the development of blood-based liver cancer screening methods, there have been few successful cases in the past,” said Professor Zhang Kang. “The only blood test (AFP method) has low sensitivity, which limits its clinical application.”

Liquid biopsy can find clues to cancer from the blood (Source: Inivata)

Recently, ctDNA-based liquid biopsy technology has become a hot topic. ctDNA is a fragment of genetic material secreted by tumor cells into the blood. According to Dr. Zhang Kang, these liquid biopsy methods have several potential advantages over other cancer detection methods. First of all, they are minimally invasive. They can be done at any time during the treatment, which allows the doctor to monitor molecular changes in the tumor in real time. Second, they can detect tumors that are not apparent or uncertain in imaging. Finally, ctDNA can reveal all aspects of a patient's tumor, and a tumor biopsy can only reveal the condition of the sampled part.

In this study, a team of two Chinese scholars focused on the methylation detection of ctDNA. Methylation is a form of regulation of gene expression that affects cell growth and changes. In tumor cells, methylation of tumor suppressor genes often occurs, thereby shutting down the functions of these tumor suppressor genes, leading to cancer development. Researchers are keenly aware that we may be able to use this in reverse to analyze whether the cells have been cancerous by analyzing the methylation of these key genes. The advantage of this technique is that the occurrence of these methylations often occurs early in cancer. Therefore, if you can accurately find these methylation sites that predict cancer, you can find the clues of cancer in the very early stage.

Part of the laboratory of Professor Xu Ruihua (Source: Sun Yat-Sen University)

But the development of this technology has a big difficulty. The amount of ctDNA in the blood is extremely low. If you want to find a methylation site that predicts cancer, it is as easy to find a specific person in the flow of people in the Spring Festival. Through continuous exploration and cooperation, Professor Xu Ruihua and Professor Zhang Kang's team developed a technique for stable separation of trace ctDNA, amplification and sequencing of methylation sites, and statistical analysis of large amounts of data.

In this study, the scientists recruited 1098 patients with hepatocellular carcinoma and 835 normal subjects and analyzed the methylation status of more than 400,000 candidate sites in their body. Using machine learning and statistical methods to check the alignment, they successfully found 10 sites that could be used for early diagnosis and 8 sites associated with patient prognosis. These sites are highly sensitive and specific and can be used for early diagnosis and prognosis assessment of liver cancer patients. Sun Yat-sen University’s news said that “it’s like cracking the 'identity fingerprint' of liver cancer, so that even the very early liver cancer lesions are invisible.”

A methylation site that can be used for early detection of hepatocellular carcinoma (Source: Nature Materials)

“Our results are very encouraging,” said Dr. Zhang Kang. "In large clinical cohorts, our diagnosis of hepatocellular carcinoma is highly correlated with tumor burden, treatment response, and cancer stage. Currently, oncologists have limited methods for detecting hepatocellular carcinoma and evaluating treatment prognosis, and our study suggests A new, more effective diagnostic method for solid malignancies. This method may also be applicable to other tumors."

We are grateful to the two Chinese scholars for their breakthrough contributions in the early diagnosis of liver cancer. This tool is of great significance to patients and is expected to help them diagnose liver cancer early and perform early treatment. In recent years, Chinese scholars have made breakthroughs in the field of life sciences, which makes people happy. In the future, we also look forward to hearing more good news from Chinese scholars!

Reference material

[1] Liquid biopsy may be new way to detect liver cancer earlier, easier

[2] Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma (Nature Materials, 2017, doi:10.1038/nmat4997)

Source: Academic Jingwei

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