|Researchers Discover New Biomarker for Predicting Liver Cancer Spread and Survival
New research has shown that a unique pattern of microRNAs, small
RNA molecules that regulate gene activity, can accurately predict
whether liver cancer will spread and whether liver cancer patients
will have shorter or longer survival, even patients with early
stage disease. The study, which appeared online January 7,
2008 in Hepatology, was conducted by researchers at the
National Cancer Institute (NCI), part of the National Institutes
of Health, and colleagues at Ohio State University, Columbus, 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, Ph.D., a staff scientist in the laboratory
of Xin Wei Wang, Ph.D., 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, have been implicated in various aspects
of human disease, including cancer. Their abundance in different
tissues and cancer types indicate that miRNAs are functionally
significant and have the potential to be used as cancer biomarkers.
Since 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 the spread of cancer,
which is known as metastasis.
In this study, Budhu and her colleagues used miRNA microarray
techniques, which allows researchers to examine the
expression of thousands of genes simultaneously. They
analyzed the miRNA expression profiles (shows the extent to
which individual miRNAs are turned on or off) in cancerous
and noncancerous 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 to tumors without metastasis. MiRNAs
are capable of regulating the expression of one or more genes,
including cancer-related genes, potentially affecting multiple
cell functions that could lead to malignancy.
"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
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 to those without the profile.
This latest finding in hepatocellular carcinoma, or HCC, in combination
with earlier research by this team on early stage HCC and the tumor
microenvironment, suggests a real potential for increasing the
accuracy of liver cancer diagnosis and prognosis, as well as in
"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
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 and occurs twice as often in men as in women. HCC 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.
For more information about cancer, please visit the NCI website
or call NCI's Cancer Information Service at 1-800-4-CANCER
For more information on Dr. Wang's research, go to http://ccr.cancer.gov/staff/staff.asp?profileid=5764.
For more information on Dr. Budhu's research, go to http://ccr.cancer.gov/staff/staff.asp?profileid=6709.
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.
Budhu A, Jia H, Forgues M, Liu C, Goldstein D, Lam A, Zanetti KA, Ye Q,
Qin L, Croce CM, Tang ZY, Wang, XW. Identification of Metastasis-related
MicroRNAs in Hepatocellular Carcinoma HEP-07-1296. Hepatology.
Online January 7, 2008. Vol. 47 No. 1.
Budhu A, Forgues M, Ye Q, Jia H, He P, Zanetti KA, Kammula US, Chen Y,
Qin L, Tang Z, and Wang XW. Prediction of venous metastases,
recurrence and prognosis in hepatocellular carcinoma based on a unique
immune response signature of the liver microenvironment. Cancer
Cell. August 2006, Vol. 10, Issue 2.