专访丨日本Eiso Hiyama教授：儿童恶性肝母细胞瘤的分子背景及潜在应用

英文原文：（上下滑动查看更多）

<Hepatology Digest>: Hepatoblastoma is the most common pediatric liver malignancy. Could you please briefly describe the characteristics of the disease? 

Dr Hiyama: Hepatoblastoma is a childhood malignancy and does not occur in adults. The disease is usually diagnosed when less than 3 years of age, and is detected from abdominal distention and liver dysfunction. The prognosis is very different to hepatocellular carcinoma in other patients. This disease is curable. We usually treat by liver resection, especially using preoperative chemotherapy to allow tumor resection. The prognosis is very good with 80-90% 5-year disease-free survival where the tumor is located only in the liver.

But sometimes distant metastases occur, particularly to the lungs. This is a critical problem in hepatoblastoma - the control of pulmonary metastases. If pulmonary metastases decrease with preoperative chemotherapy of the primary hepatic tumor, then the prognosis is high, but if not controlled with chemotherapy, the prognosis is much worse. So we are now searching for biomarkers before chemotherapy. If we can distinguish the molecular background of the hepatoblastoma in the hepatic cell, we can use the appropriate chemotherapy regimen.

英文原文：（上下滑动查看更多）

<Hepatology Digest>: The prognosis of patients with hepatoblastoma varies greatly. Accurate malignancy stratification of hepatoblastoma is of great significance for improving the prognosis of patients. What biomarkers or models are currently available for risk stratification of hepatoblastoma?

Dr Hiyama: This is the most critical problem for us now. We currently have no clinical biomarkers for the risk stratification and staging of hepatoblastoma. We stratify risk only by the stage or age or serum liver enzyme levels or pathological findings. But we have not found a useful biomarker for the risk stratification of hepatoblastoma, and we are searching for that now. Some local hepatoblastomas progress aggressively. On the other hand, a patient with lung metastases can have a favorable prognosis if cisplatin chemotherapy is effective on the pulmonary lesions. We can know this prior to treatment with a useful biomarker.

英文原文：（上下滑动查看更多）

: Understanding the molecular background of the clinical and phenotypic diversity of hepatoblastoma can not only provide the neces sary clues for precise risk stratification, but also potential therapeutic targets for clinical treatment. Could you please talk about your findings in this regard? 

Dr Hiyama: This is an interesting topic, and provides clues to risk stratification and the treatment of high-grade hepatoblastoma. Some hepatoblastomas occur in premature babies born at less than 1500 grams. This is a high-risk population for hepatoblastoma. I don’t know why premature babies have higher risk of hepatoblastoma, and now we are searching for clues. We are comparing the differences in mutation status between premature infants and normal-term babies, including molecular and genetic factors.

As you know, the imprinting status is correlated to pediatric oncology with hepatoblastoma, as well as neuroblastoma. We are looking at changes at the 11p chromosome near the IGF2 gene or H19 gene. Changes at these sites may be correlated to hepatoblastoma occurrence. This imprinted long non-coding RNA may be a useful therapeutic target.

英文原文：（上下滑动查看更多）

<Hepatology Digest>: What related research work is your team doing?

Dr Hiyama: We are now analyzing the full genome sequencing of around 200 hepatoblastoma cases. There are differences in the mutation status of hepatoblastoma samples and background or normal liver tissue. Hepatoblastomas show fewer mutations than all other cancers - the number of mutations is very low in hepatoblastomas. So we are focused on the mutation status as well as non-coding RNA status, to stratify for hepatoblastoma occurrence and progression.