Serological Marker Panel(S) for Early Detection of Pancreatic Ductal Adenocarcinoma: Discovery and Prospective Study

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies in the world, with a very low (＜5%) 5-year survival rate after diagnosis. Since chemotherapy and radiotherapy failed to significantly improve the poor prognosis and survival rate of PDAC patients, there is an urgent need for identifying better diagnostic markers for early detection of PDAC. There is a growing consensus that effective and accurate detection of early stage cancer will likely rely on marker panels that have greater specificity and sensitivity than each marker alone. Recently, we have developed a cancer cell secretome-based strategy to identify potentially useful serological markers for nasopharyngeal carcinoma, colorectal carcinoma, oral cancer and non-small cell lung cancer (Proteomics 5, 3173-82, 2005; Proteomics 8, 316-32, 2008; Proteomics-Clin. Appl. 2, 1586-95, 2008; J. Proteome Res. 7, 3765-75, 2008; J Proteome Res, 8, 4428-40, 2009). For PDAC, we have recently identified phosphoglycerate kinase 1 (PGK1) and brain-type glycogen phosphorylase (BGP) as PDAC serum markers via mass spectrometry-based proteomics study of cancer tissue and cancer cell secretome, respectively (Proteomics 6, 2259-72, 2006; Yu et al., manuscript in preparation). Moreover, we have generated a comprehensive cancer cell secretomes of 23 cancer cell lines derived from 11 cancer types (including two PDAC cell lines, MIA-PaCa-2 and PANC1) by 1D SDS-PAGE in combination with LC-MS/MS (the GeLC-MS/MS method). A total of 31,180 protein identities accounting for 4,584 non-redundant proteins were detected in this dataset, with an average of ~1,300 proteins per cell line (Wu et al., Mol Cell Proteomics in revision). We have detected 1035 and 1609 proteins (based on the detection of at least two peptides per protein) in the secretome of PANC1 and MIA-PaCa-2 cells, respectively, which represents a valuable reservoir for the discovery of potential serological cancer biomarkers. In this proposal, we plan to perform prospective study to evaluate clinical application of the previously identified serum markers, namely, PGK1 and BGP, as compared to the currently used PDAC serological marker CA19-9. In addition, we plan to identify and validate other potentially useful PDAC serological marker panel(s) by integration of PDAC cancer cell secretome (our in-house dataset), tissue transcriptome, tissue microarray and quantitative serum databases (retrieved from public domains). Clinical specimens (including PDAC tissue specimens and blood samples from healthy controls, patients with pancreatitis and PDAC patients) and patients’ data will be obtained through collaboration with Department of Surgery, Chang Gung Memorial Hospital and Department of Surgery, Taipei Veterans General Hospital. Finally, we plan to incorporate the Bio-Plex suspension array system --- a microscopic bead-based, multiplexed and highly sensitive biomarker quantification platform --- to quantify and validate the marker panel(s) we have found in blood samples from healthy controls, patients with pancreatitis and PDAC patients in a high throughput format.

Project ID:PC10001-1127
External Project ID:NSC99-2320-B182-017-MY3