Teasing Out The Three Subtypes Of Liver Cancer

By combining genomic data with information about patients’ immunological status, scientists in Japan can now better characterize hepatocellular carcinoma.

AsianScientist (Feb. 14, 2019) – A research team based at Tokyo Medical and Dental University (TMDU), Japan, has combined genomic and immunological data to classify hepatocellular carcinoma (HCC), the most common type of liver cancer, into three distinct subgroups. They reported their results in EBioMedicine.

Liver cancer remains a major healthcare problem globally. It is the second most common cause of cancer-related deaths, and previous studies have shown that the predominant form of liver cancer—HCC—is highly heterogenous, which means that treatments that work in one patient may not be effective in another.

Scientists have sought to better characterize HCC. However, their efforts have been limited by an inability to integrate data from various sources into a single classification system.

In this study, a research team led by Professor Shinji Tanaka at TMDU combined data on mutations, gene expression patterns and immunological status to shed light on the variation among cases of HCC. The researchers first extracted a range of data on 183 surgically removed HCC tumor specimens and used statistical analysis to see if the samples clustered together into specific groups with distinct features.

Next, they tested whether their findings were supported by an additional analysis of data from 373 HCC patients that incorporated data on each patient’s characteristics, such as their clinical course and overall outcome.

“We knew that we’d have to take a large number of different variables into account in order to establish clinically useful stratification of HCC,” said Tanaka, adding that “our combination of genomic, epigenomic and transcriptomic data and immune system characterization provided new insights into this disease.”

The researchers revealed three types of HCC with their classification method. The first was characterized by tumors with mutation in the CTNNB1 gene and immune suppression. A second type featured tumors associated with conditions such as obesity, diabetes and dyslipidemia in the absence of hepatitis virus infection. Finally, the third group included fast growing tumors with genomic instability. Patients with tumors belonging to the third group had a worse prognosis.

“If we can use this new classification to group HCC patients according to their subtype, it should help us provide the specific treatment that’s best for them,” said lead author Assistant Professor Shu Shimada of TMDU. “Our finding of a metabolic disease-related subtype is also particularly important given the rate at which diseases such as obesity and diabetes are becoming more prevalent.”



The article can be found at: Shimada et al. (2018) Comprehensive Molecular and Immunological Characterization of Hepatocellular Carcinoma.

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Source: Tokyo Medical and Dental University; Photo: Shutterstock.
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