About Gastric Cancer (Biomarkers) Knowledgebase

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Overview >>
Gastric adenocarcinoma is the second leading cause of cancer death worldwide. It is
particularly common in Asia and especially in China and Japan. In Singapore it is the
fourth most common cancer in males who have a 1:50 lifetime risk of developing gastric
cancer. Gastric cancer traditionally carries a poor prognosis with 79% of tumors
diagnosed at stage IV and five year survival less than 5%. Advanced gastric cancer is
generally refractory to chemotherapy, which leads to poor prognosis. It has been shown
that if it is diagnosed at an early stage, it is a curable disease. Therefore it is most
important to be able to identify clinically useful early markers that can detect gastric
cancer at an early stage.
Aims
This knowledgebase integrates available information from various sources to help

find out the genes responsible for the formation of gastric cancers

identify better diagnostic and prognostic biomarkers for gastric cancers

Gastric cancer prognostic factors used in clinical practice

depth of invasion through the gastric wall

the presence or absence of regional lymph node involvement

Molecular biomarkers for diagnosis and prognosis of gastric cancer

Carcinoembryonic antigen (CEA)

CA 125, CA 19-9, CA 72-4 and alpha-fetoprotein (useful for prognosis)

Serum pepsinogen I (predictor of stomach cancer)

proteases (pepsinogen C, plasminogen activator, matrix metalloproteinases and

their inhibitors)

cadherins, mucins and CD44 splicing variants (related to invasion/metastasis and

extracellular matrix adhesion and degradation)

Genetic changes associated with gastric cancer oncogenesis

genetic instability represented by microsatellite instability (CA repeats)

re-activation of telomerase activity

inactivation of tumour suppressor genes

activation of oncogenes

Major classes of genes associated with the progression of gastric cancer

Genes related to growth signal
Genes related to cell cycle regulation
transduction
Cyclins
(cyclin E was found to serve as a useful
prognostic indicator for gastric cancer
progression)

Epithelial growth factor (EGF)

transforming growth factor (TGF-)
and TGF- They serve as autocrine
growth factors and associated with
gastric cancer progression.

p53
(Mutated p53 isoforms can generate an
autoimmune response. Serum anti-p53
antibodies can serve as a diagnostic and
prognostic marker in gastric cancer
patients.

Vascular endothelial growth factor

(VEGF)
independent prognostic marker in gastric
cancer patients. Together with plateletderived endothelial cell growth factors
(PD-ECGFs), it has become a novel
gastric cancer prognostic marker.

Cdks
(Regulators cyclin-dependent kinases
(CDKs 1, 2, 4 and 6) and their inhibitors
(p15, p16, p21waf1/cip1 and p27kip1) are also
expressed in gastric cancer tissues.

Protein tyrosine kinases (PTKs)

Receptors for the growth factors and
they are key molecules in signaling
pathways such as phosphoinositide 3kinase, 70 kDa S6 kinase, mitogenactivated protein kinase (MAPK),
phospholipase C-gamma, and the
Jak/STAT pathways. PTKs are good
candidates to examine genes within a
biochemical pathway, or groups of genes
with similar functions and under
differential regulation (i.e. gene
families), as they are involved in the
growth regulation of normal cells, as
well as the oncogenesis of cancer cells.

Oncogenic receptor PTKs which have been studied in gastric cancers

c-Met [hepatocyte growth factor (HGF) Amplification of the c-met gene has been
receptor]
demonstrated in scirrhous-type gastric
cancers. c-met is overexpressed or
amplified in advanced gastric cancers of
both the well-differentiated and poorly
differentiated types. c-Met
immunoreactivity was observed at a high

positive rate (4080%). Simultaneous

detection of c-met gene expression and
c-Met protein immunoreactivity has also
been noted in the majority of gastric
cancer specimens.
k-Sam (fibroblast growth factor receptor k-sam activation is more specific to the
2)
poorly differentiated variants. k-Sam
protein was detected in ~50% of poorly
differentiated gastric cancers, and not in
differentiated-type gastric cancers.
ErbB2/Neu [EGF receptor (EGFR) 2]

By contrast, amplification of the

erbB2/neu gene is often detected in welldifferentiated gastric carcinomas. EGFR
antibodies was demonstrated in 3050%
of human gastric cancers and correlated
with a poor prognosis. ErbB2
immunoreactivity was seen in 1050%
of all human gastric cancers, and was
more common in well-differentiatedtype gastric cancers. The expression of
the ErbB2 protein is a significant
independent prognostic factor for longterm survival, disease recurrence and
lymph-node metastasis Targeting erbB2expressing cells with conjugated
immunoliposomes containing
chemotherapeutic reagents might prove
useful.

Src
VEGF receptor (KDR)
Hek5 (Erk)
Abl, nerve growth factor receptor
(TrkA)
Stem cell factor receptor (c-Kit)

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