A unique pattern of microRNA molecules, which are associated with regulation of gene expression, can accurately predict risk of metastasis of hepatocellular carcinoma and survival of patients, even when the disease is in an early stage, according to an article published online January 7 by Hepatology.

The work was done collaboratively by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues at Ohio State University, Columbus, Ohio, and the Liver Cancer Institute in Shanghai, China.

"The aggressive nature of hepatocellular carcinoma, a prevalent type of liver cancer, is largely due to its tendency to spread or recur after surgery," said the study's lead author, Anuradha Budhu, PhD, a staff scientist in the laboratory of Xin Wei Wang, PhD, head of the Liver Carcinogenesis Section of NCI's Center for Cancer Research (CCR).

"Identifying new diagnostic and prognostic biomarkers for liver cancer is a first step in alleviating the dismal outcome of this disease."

MicroRNAs, or miRNAs, had previously been implicated in various aspects of human disease, including cancer. Their abundance in different tissues and cancer types indicate that they are functionally significant and have the potential to be used as cancer biomarkers. Because miRNAs can effectively regulate the activity of multiple cancer-related genes and pathways, they are prime candidates for coordinating the intricate events that lead to metastasis.

In the current study, Budhu and her colleagues used miRNA microarray techniques to simultaneously examine expression of thousands of genes. Analysis of miRNA expression in malignant and benign liver samples from 131 patients with or without metastasis who underwent surgery at the Liver Cancer Institute and Zhongshan Hospital in Shanghai. The analysis revealed a set of 20 miRNAs with different patterns of expression in tumors with metastasis compared with tumors without metastasis.

"This is an important and unique finding because it is the first study to show that miRNAs play a significant role in liver metastasis," explained Budhu. "In fact, miRNAs have not previously been related to cancer spread in any other organ."

Using the new gene expression profile, the researchers found that patients with the metastasis-miRNA profile had a two-fold higher risk of shorter survival compared with patients without the profile. This latest finding in hepatocellular carcinoma, in combination with earlier research by the same team on early-stage hepatocellular carcinoma and tumor microenvironment, suggests real potential for increasing the accuracy of liver cancer diagnosis and prognosis, as well as in monitoring recurrence.

"MiRNAs are also very stable molecules, which is an ideal property that could allow for more dependable measurements in clinical diagnostic or prognostic methods. Since miRNAs can affect multiple genes, including those related to cancer, they are also promising new targets for therapeutic approaches to liver cancer treatment," said Budhu.

Hepatocellular carcinoma is the most common liver cancer diagnosed in adults and has a high prevalence in Asian and African populations. The rate of new cases has been rising over the past 10 years in the United States and occurs twice as often in men as in women. It is a very aggressive disease; patients usually survive less than one year after diagnosis. In 2007, an estimated 19,160 Americans were newly diagnosed with liver cancer and an estimated 16,780 people died of the disease.