Secretome-based identification of serum biomarkers for pancreatic cancer detection

• Main Authors: Ya Ting Chang, 張雅婷
• Other Authors: J. S. Yu
• Format: Others
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/15587098528894262243

博士 === 長庚大學 === 生物醫學研究所 === 100 === Pancreatic cancer is the tenth leading cause of cancer death in Taiwan and the fourth in the United States. The five-year survival rate is less than 5% because of its late diagnosis and resistance to various treatments. Current diagnosis based on imaging or endoscope methods is very limited in early diagnosis. Even the usage serological tumor marker, CA19-9, also presents limited specificity and sensitivity. We propose to use an established cancer cell secretome database combined with efficiently analysis strategy to find out candidate proteins to be a potential pancreatic cancer marker for early detection or diagnosis. Two pancreatic cancer cell lines, PANC-1 and MIA PaCa-2 were used in pancreatic cancer cell secretome profiling. Integrated analysis strategy was performed to concentrate candidate proteins. With preliminary verification, four proteins presented highly potential as the detection markers for pancreatic cancer. Immunohistochemical analyses revealed elevated expressions of all four proteins in pancreatic cancer tissues compared with paired adjacent non-cancerous tissues (n = 31-67). The serum levels of two proteins among all pancreatic cancer patients (n = 154) and in early-stage cancer patients (n = 35-108) were significantly different with those in healthy controls (p < 0.0001). The combination of the two proteins and CA 19-9 outperformed each marker alone in distinguishing pancreatic cancer patients from healthy persons. These data revealed high potential of the two proteins as serological biomarkers for pancreatic cancer detection. Furthermore, an iTRAQ-based quantitative analysis was performed on one of the four proteins, endoplasmic reticulum oxidoreductin 1-like (ERO1L) knock-down cells to evaluate the role of ERO1L in pancreatic cancer. A comprehensive analysis showed that the amount of proteins identified in conditioned media was dramatically changed when ERO1L was knocked down in pancreatic cancer cells. This finding supports the role of ERO1L functions in regulation of protein secretion in pancreatic cancer cells.