IDENTIFICATION OF BIOMARKERS FOR COLORECTAL CANCER FROM MALAYSIAN PATIENTS

Loading...
Thumbnail Image
Date
2010-06
Authors
YEOH, LAY CHIN
Journal Title
Journal ISSN
Volume Title
Publisher
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.
Description
Keywords
BIOMARKERS , COLORECTAL CANCER
Citation