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Title: Discovery of early serum biomarkers of gastric cancer in a rat model
Authors: Lam, Wing-kei
Degree: M.Phil.
Issue Date: 2009
Abstract: Gastric cancer has significant morbidity and mortality worldwide. According to the World Health Organization, stomach cancer, which accounts for 866,000 deaths, is the second most common cause of cancer-related death world-wide in 2007. Early diagnosis has a proven impact on improving disease outcome compared with generally poor prognosis after disease progression. Thus, early detection of dysplasia is crucial. The most widely used screening procedures for gastric cancer include endoscopy and biopsy. However, as these invasive screening methods are physically discomfort, they are not suitable for large-scale screening purposes. Therefore, non-invasive serum- or plasma-based diagnostic screening for early gastric cancer detection are likely to be far more acceptable than the current screening options and would likely greatly increase the percentage of the population screened. The most frequently used gastric tumor markers are carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), alpha-fetoprotein antigen (AFP) and human chorionic gonadotropin (hCG). However, they are not sensitive biomarkers as only a modest proportion of patients with gastric cancer have elevated levels of these proteins. Therefore, there is an urgent need for specific biomarkers indicative of early gastric cancer for diagnostic purposes. New emerging proteomic technology using high resolution two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) provides a promising option. One of the major hindrances of biomarker discovery is the presence of high abundance proteins. Some abundant proteins such as albumin, immunoglobulins, haptoglobin, antitrypsin and transferrin constitute around 90% of all protein masses present in serum samples. These proteins mask over the relatively low abundance proteins, resulting in difficulties in discovering candidate biomarkers. Another hurdle for early biomarker discovery will be the availability of early stage gastric cancer samples. It should be stressed that when gastric cancer diagnosed by classical endoscopy or biopsy method, it is already in the late stage. Therefore, in this study, rat gastric cancer was induced experimentally. Serially serum samples were taken and these rats were examined periodically by high resolution mammography to check for gastric lesion. It was intended to correlate possible gastric lesion seen with differentially expressed proteins found in the serum samples. The removal of high abundance proteins by a customized immunoaffinity column was also attempted. Comparative proteomic analysis was used to search for characteristic alternations in the sera of rats with dysplasia and early adenocarcinoma. The various stages of stomach carcinogenesis were confirmed by histological examination. Finally, a panel of serum candidate biomarkers was identified by MALDI-TOF-TOF mass spectrometry. Some of these biomarkers had not been reported to be related to gastric cancer.
Subjects: Hong Kong Polytechnic University -- Dissertations
Stomach -- Cancer
Tumor proteins -- Analysis.
Rats as laboratory animals
Pages: xvii, 200, [13] p. : ill. (some col.) ; 30 cm.
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