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Scientists
Identify Specific Markers that Trigger Aggressiveness
of Liver Cancer
Patients
with positive epithelial-mesenchymal transition
markers have lowest survival rate
Hepatocellular
carcinoma (HCC) or primary liver cancer forms
in the epithelial tissue of the liver and is most
commonly caused by the hepatitis B virus (HBV)
or hepatitis C virus (HCV). In the U.S., the National
Cancer Institute (NCI) estimates that 15,000 men
and 6,000 women are diagnosed with HCC each year.
Worldwide, HCC accounts for 632,000 cases with
the highest regions being Western Pacific and
Africa according to a 2004 World Health Organization
(WHO) report.
Researchers
from Taipei Veterans General Hospital investigated
the molecular mechanisms of HCC, one of the most
common tumors found in Taiwan and largely caused
by the high prevalence (15%-20%) of HBV in the
country. The study, funded in part by a grant
from the National Science Council, is the first
to provide a comprehensive profile of multiple
Epithelial-Mesenchymal Transition (EMT) markers
and to demonstrate that Snail and Twist, but not
Slug, are the major inducers of EMT in HCC. Results
of the study are published in the November issue
of Hepatology, a journal of the American Association
for the Study of Liver Diseases.
EMT
is critical in the development of invasiveness
and metastatic potential of human cancers, and
described as process where epithelial cells no
longer adhere to one another, taking on fibroblastic
properties. The EMT process is initiated by suppression
of E-cadherin function through the major EMT regulators
(Snail, Slug, and Twist). E-cadherin (calcium
dependent adhesion molecules) is a type of protein
found in the epithelial cells that ensure tissue
cells bind together. When E-cadherin function
is lost, cancer is able to progress and metastasize.
Professor
Jaw-Ching Wu and colleagues obtained samples of
primary HCC with adjacent non-tumorous liver tissues
from 123 patients who had hepatic resection surgery
between 1990 and 2002 at Taipei Veterans General
Hospital. Reduced E-cadherin function was observed
in 60.2% of patients. "We found a significant
decrease in cancer-free intervals and overall
survival for those patients who had a reduction
in E-cadherin function," explained Dr. Wu.
A downregulated expression of E-cadherin was also
associated with large tumor size and multi-nodular
tumors.
Results
show that co-expression Snail and Twist (transcription
factors or proteins that control when genes are
switched on or off) indicates the worst prognosis
for HCC patients. "Our research is the first
to prove that the two proteins (Snail and Twist)
work independently, but together promote EMT,"
noted Dr. Wu.
According
to the study, overexpression of Twist is correlated
with HCV-related HCC, partially explaining the
highly invasive behavior and poor prognosis for
patients with this form of liver cancer. Dr Wu
added, "Our results provide essential information
for determining HCC prognosis in patients and
identifies possible new treatments for future
HCC management."
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