By AMY ADAMS
Cancerous liver cells rely on a different set of genes than normal liver cells in order to function. Now researchers at the medical center have identified genes needed by cancerous liver cells but ignored or used at different levels by normal liver cells.
The discovery could lead to better treatments and screening tests for liver cancer, which is often not detected until the disease is too advanced to treat effectively.
A screening test would be of particular benefit to Asian and Pacific Island populations, which have 10 times the risk of liver cancer than Caucasians because of high rates of chronic hepatitis B infection.
"There's a real opportunity to use this information to develop better and cheaper tests for diagnosis and treatments," said Samuel So, MD, director of Stanford's Asian Liver Center and an associate professor of surgery at the School of Medicine. Last year, So launched the Jade Ribbon Campaign to draw attention to the high rate of hepatitis B among Asian Americans. Chronic hepatitis B infection can lead to liver cancer.
Surgically removing the tumor is considered the only effective treatment for liver cancer, but less than 20 percent of liver cancer patients are diagnosed when surgery is still an option. Of those who undergo surgery, 50 percent experience a relapse. "Most of the time, if you wait until the patient has symptoms, the diagnosis is too late," said So, who also oversees the medical center's liver cancer program. Because of late discovery, he added, many liver cancer patients survive only four to six months after diagnosis.
To identify the genes in this study, So and his colleagues compared the genes being used in more than 200 normal and tumor samples. First they isolated RNA from the samples (RNA is produced by active genes -- the more active the gene, the more RNA is produced). Then they tacked a fluorescent molecule onto the RNA and washed it over the surface of a glass slide dotted with 17,400 human genes. Any RNA that corresponded to a gene on the array stuck, creating a fluorescent spot. A brighter spot meant more RNA and more gene activity.
By comparing the pattern of fluorescent spots created by both normal and tumor samples, the researchers determined which genes were being used at either high or low levels in the tumor samples. They reported these findings in the June issue of the journal Molecular Biology of the Cell. Many of the genes they found were well-known cancer genes; however, "many were not known to play a role in liver cancer," So said.
Of these, he hopes to find genes that make proteins that are secreted from the tumor and are present in the bloodstream of individuals with liver cancer.
"If that protein is only present or produced in high levels in people with liver cancer, maybe we can develop a better blood test to detect the cancer," So said. He added that other proteins could be targets for new drugs to treat the disease once it's diagnosed.
So said many Asians are exposed to hepatitis B at birth and roughly 10 to 15 percent become chronic carriers of the disease. Overall, 400 million people worldwide have chronic hepatitis B. Although infected individuals may feel healthy, the disease can cause scarring of the liver (cirrhosis) or liver cancer in people as young as 30. So recommends that all Asian Americans be screened for hepatitis B and get vaccinated if they test negative.
Hepatitis B carriers should be screened for liver cancer every six months by having their blood tested for a protein called alpha-fetoprotein, which is sometimes at higher levels in people with liver cancer. These individuals also should undergo a liver ultrasound annually to look for tumors. So said neither technique is completely accurate nor are the precautions inexpensive enough for widespread use in poor countries, highlighting the need for a better screening tool.
So's colleagues include Xin Chen MD, PhD, research associate at the Asian Liver Center and the department of surgery; Pat Brown MD, PhD, professor of biochemistry; David Botstein, PhD, professor of genetics; Chris Barry, MD, PhD, resident in surgery; and his collaborators from the University of Hong Kong. Other Stanford investigators are John Higgins, MD, assistant professor of pathology; Matt van de Rijn, MD, PhD, associate professor of pathology; and Kin-man Lai, MD, resident in surgery.
Stanford Report, June 12, 2002