IDENTIFICATION OF BIOMARKERS FOR COLORECTAL CANCER FROM MALAYSIAN PATIENTS
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Date
2010-06
Authors
YEOH, LAY CHIN
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Abstract
Colorectal cancer (CRC) is on the rise. However, biomarkers for
indication of CRC progression is still lacking despite several advances in
proteomic and microarray tools. This study aims to identify potential biomarkers
for the diagnosis of CRC among Malaysian patients. In this study, sequential
extraction was first performed using Tris buffer followed by TLB buffer in order
to reduce the complexity of the CRC proteome. The tissues used were surgical
resections of normal mucosa and cancerous tissues from 26 CRC patients. The
extracted proteins were separated by 2D gel electrophoresis. The differentially
expressed protein spots were then mapped for further protein identification by the
use of liquid chromatography tandem mass spectrometry (LC-MS/MS). We have
identified 37 hydrophilic proteins in the Tris extracts and 24 hydrophobic
proteins in the thiourea lysis buffer (TLB) extracts from the samples collected.
Leukocyte elastase inhibitor (LEI) and 60 kDa heat shock protein (HSP60) were
the potential biomarkers for CRC analyzed from the Tris extracts whereas
triosephosphate isomerase (TPI) and annex in A3 were the potential biomarkers
for CRC analyzed from the TLB extracts. Moreover, LEI was the potential
biomarker for CRC patients at stage III in combination with either moderately
differentiated adenocarcinoma (MDA), well differentiated adenocarcinoma
(WDA) or lymph node metastasis CRe. Fibrinogen beta chain (FIBB) was a
good biomarker in CRC patients at stage II and MDA. We also noted distinctive
protein expression patterns among the three races. TPI was the potential
biomarker in CRC patients at stage III in combination either with MDA, WDA or
lymph node metastasis CRe. Stage II and MDA CRC tissues revealed annexin
A3 as a useful biomarker. TPI and annexin A3 were found commonly expressed
in the three races (Chinese, Malay and Indian), reflecting the importance of these
biomarkers in CRC amongst Malaysian patients. Immunostaining results of
calreticulin and heat shock 70 kDa protein (HSP70) on HT29 and HCTl16 colon
cell lines revealed the cellular location of these proteins on the external surface of
cell membranes. Principal component analysis (PCA) and linear discriminant
analysis (LDA) reflected the significance of these differentially expressed
proteins in indicating the state of cancer in tissues.
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Keywords
BIOMARKERS , COLORECTAL CANCER