|Researchers Discover a Unique Pattern of Gene Activity that
Can Predict Liver Cancer Spread
Researchers have found that a unique pattern of activity for genes in cells
located in the tissue surrounding a liver tumor can accurately predict whether
the cancer will spread to other parts of the liver or to other parts of the body.
This preliminary research was led by a team of researchers*,
including several from the National Cancer Institute (NCI), part of the National
Institutes of Health (NIH), and other institutes, who report these findings in
the August 2006 issue of Cancer Cell **.
“Research into the role of inflammation in hepatocellular carcinoma, a type
of liver cancer, is very important because inflammation is one of the first lines
of defense mobilized by the immune system in response to tissue injury or infection.
A better understanding of the inflammatory process will hopefully lead to better
treatments for this deadly disease,” said NIH Director Elias A. Zerhouni, M.D.
“Persistent and extensive inflammation of the liver is a common problem in hepatocellular
carcinoma, or HCC, patients,” said Xin Wei Wang, Ph.D., head, Liver Carcinogenesis
Unit at NCI’s Center for Cancer Research and study leader. “We wanted to examine
the role that the large number of immune cells in the liver may play in supporting
spread of the tumor.”
“The tendency of hepatocellular carcinoma tumors to metastasize or recur following
surgery contributes to the poor outcome associated with this disease,” said NCI
Acting Director John E. Niederhuber, M.D. “Accurately predicting this cancer’s
risk of spread will help doctors decide on the best options to use in treating
Researchers analyzed gene expression signatures — patterns of gene activity — largely
in immune cells within the liver microenvironment, which is the area immediately
surrounding the tumor. The set of 17 genes included those that encode the messages
for cytokines, which are small proteins produced by immune cells that are used
to communicate messages between cells in the immune system to either turn up
or down the immune response.
From the 17-gene set, researchers identified a unique pattern in the immune
cells found in normal tissue of the liver microenvironment that could predict
the potential for liver tumor metastasis. This metastasis-specific profile included
gene activities responsible for increased production of certain cytokines that
are associated with an anti-inflammatory response, as well as suppression of
immune response. Increased levels of these cytokines are associated with a poor
prognosis of cancer.
“When we used the gene signature of immune cells in the liver, we could predict
tumors that would metastasize in 92 percent of the samples we studied,” said
Wang. “This is the first example where we can stratify HCC patients to identify
those who would benefit from certain post-surgical treatments to prevent metastases
The 115 HCC patients included in the study were being treated at the Zhongsham
Hospital, Shanghai, China. Fifty-two patients had tumors that had metastasized
within the liver or to other organs, and 63 had tumors that had not metastasized.
Samples from 22 patients with chronic liver disease and from eight normal livers
were also studied as controls.
“We previously identified gene signatures in the liver tumor that could accurately
predict the tumors that were capable of metastasis in 78 percent of the cases
we studied,” explained Wang. “This study is different because the immune cells
associated with this signature are in the patient’s normal liver tissue — the
microenvironment of the tumor. With this microenvironment gene signature, we
could predict metastatic disease in 92 percent of the samples.”
HCC is the most common liver cancer diagnosed in adults and has a high prevalence
in Asian and African populations. The rate of new HCC cases has been rising over
the past 10 years in the United States. HCC is a very aggressive disease; patients
usually survive less than one year after diagnosis. HCC occurs twice as often
in men as in women. In 2006, an estimated 18,500 Americans will be newly diagnosed
with liver cancer and an estimated 16,200 will die of the disease.
For more information on Dr. Wang's research, go to http://ccr.cancer.gov/staff/staff.asp?profileid=5764.
For more information about cancer, please visit the NCI Web site at http://www.cancer.gov,
or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit www.nih.gov.