- 學位論文
The Application of Proteomic Analysis in Gastric Cancer Plasma Protein Biomarker Discovery
The Application of Proteomic Analysis in Gastric Cancer Plasma Protein Biomarker Discovery
摘要
Background: Gastric cancer is the third most common cause of cancer death after lung and liver cancer which causes approximately 800,000 deaths in 2012. Development of plasma biomarkers into screening, diagnostic, prognostic and treatment monitoring tool has shown promising results in improving the management strategy of certain types of cancer. However, in gastric cancer, the use of plasma biomarkers is limited. Therefore, this study is aimed to discover novel plasma protein biomarkers for gastric cancer which may be further developed into screening, diagnostic, prognostic and treatment monitoring tools. Methods: Blood plasma from 24 gastric cancer patients and 9 healthy controls were collected from TMU Hospital Biobank and were prepared for LC-MS/MS mass spectrometry assay. We further analysed the data obtained from mass spectrometry assay using PEAKS7 bioinformatic software to identify potential candidates of plasma protein biomarkers. Verification and validation of the identified biomarker candidates in different patient cohort were conducted using immunoblotting assay. Results: We found 4 potential plasma protein biomarker candidates; APOC-1, gelsolin, SHBG and CO4A which were significantly overexpressed in gastric cancer patients. Validation study using immunoblotting assay found only SHBG showed a consistent result in which the plasma expression was significantly higher in patient group (p<0.01). Area under the curve of the ROC curve for SHBG expression was 0.89 (95% CI 0.74-1.00, p<0.01). Conclusion: LC-MS/MS mass spectrometry assay is a promising tool for screening of blood plasma gastric cancer biomarkers. The plasma SHBG level has a potential as a gastric cancer biomarker and is worthy for further investigation.
並列摘要
Background: Gastric cancer is the third most common cause of cancer death after lung and liver cancer which causes approximately 800,000 deaths in 2012. Development of plasma biomarkers into screening, diagnostic, prognostic and treatment monitoring tool has shown promising results in improving the management strategy of certain types of cancer. However, in gastric cancer, the use of plasma biomarkers is limited. Therefore, this study is aimed to discover novel plasma protein biomarkers for gastric cancer which may be further developed into screening, diagnostic, prognostic and treatment monitoring tools. Methods: Blood plasma from 24 gastric cancer patients and 9 healthy controls were collected from TMU Hospital Biobank and were prepared for LC-MS/MS mass spectrometry assay. We further analysed the data obtained from mass spectrometry assay using PEAKS7 bioinformatic software to identify potential candidates of plasma protein biomarkers. Verification and validation of the identified biomarker candidates in different patient cohort were conducted using immunoblotting assay. Results: We found 4 potential plasma protein biomarker candidates; APOC-1, gelsolin, SHBG and CO4A which were significantly overexpressed in gastric cancer patients. Validation study using immunoblotting assay found only SHBG showed a consistent result in which the plasma expression was significantly higher in patient group (p<0.01). Area under the curve of the ROC curve for SHBG expression was 0.89 (95% CI 0.74-1.00, p<0.01). Conclusion: LC-MS/MS mass spectrometry assay is a promising tool for screening of blood plasma gastric cancer biomarkers. The plasma SHBG level has a potential as a gastric cancer biomarker and is worthy for further investigation.