Liver cancer may be diagnosed from altered sugar metabolism

Altered gene expression that causes cancerous cells to metabolize fructose differently from healthy cells could be a significant new biomarker for diagnosing liver cancer.
The researchers found that cancerous liver cells metabolize fructose differently to healthy liver cells.

So concludes a study led by the University of Texas MD Anderson Cancer Center in Houston and published in the journal Nature Cell Biology.

The study reveals that a gene called KHK (ketohexokinase or fructokinase) is expressed differently in cancerous versus normal liver tissue.

Senior author Zhimin Lu, professor of neuro-oncology at MD Anderson, says:

“Normal liver cells catalyze both glucose and fructose for energy, amino acid and lipid production. However, we found that liver tumors stopped using fructose. Thus, monitoring fructose metabolism could potentially be used for liver cancer diagnosis.”

Liver cancer is the tenth most common cancer in the US, where it is the fifth most common cause of cancer death among men and the eighth among women.

This year, an estimated 39,230 American adults (28,410 men and 10,820 women) will be diagnosed with primary liver cancer, and an estimated 27,170 (18,280 men and 8,890 women) will die of the disease.

‘KHK-A essential for the formation of liver tumors’

Fructose is a type of sugar that occurs naturally in plant-based foods. However, most fructose in the American diet comes not from fresh fruit, but from high fructose corn syrup that is used to sweeten soft drinks and candy.

Fast facts about liver cancer

  • Liver cancer is more common in developing countries within Africa and East Asia than in the US
  • In some countries, it is the most common cancer type
  • For the 43% of US cases diagnosed at an early stage, the 5-year survival rate is 31%.

Find out more about liver cancer

The KHK gene codes for a kinase that processes fructose. Kinases are enzymes that allow cells to transfer phosphate, a key component for producing energy and regulating proteins.

Healthy liver cells express KHK in a way that produces kinases that are very efficient at processing fructose.

But Prof. Lu and colleagues found that in the case of liver tumor cells, expression of KHK led to a variety called KHK-A that produces kinases much less able to process fructose.

They also discovered that KHK-A not only produces kinases for processing sugar, but also for processing protein, and that its protein kinase activity enhances the synthesis of DNA and RNA in tumor cells.

Thus, the study newly identifies KHK-A as essential for the formation of liver tumors, and it could serve not only as a biomarker for liver cancer diagnosis, but also as a target for treatment.

Prof. Lu concludes:

“Our study revealed a pivotal mechanism underlying how liver and liver tumor cells use fructose and highlight the instrumental role of the KHK-A protein in promoting tumor development.”

Meanwhile, Medical News Today recently learned of a study that suggests eating broccoli protects against liver cancer.

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