Discovery and Verification of Exosomal Membrane-Associated Proteins as Novel Plasma Biomarkers for Early Detection and Disease Monitoring of Colorectal Carcinoma

Colorectal cancer (CRC) is one of the most common cancers worldwide, and is currently the No.1 cancer type of cancer among men and the second most common type of cancer among women in Taiwan. Like other cancers, early detection of CRC can significantly improve patient’s outcome and reduce medial cost. However, more than half of CRC cases are diagnosed at advanced stages. In addition, for most surgical CRC patients, tumor recurrence or metastasis is still a major challenge, and earlier detection of tumor recurrence may give physicians a window of disease management. Although numerous biomarker candidates have been discovered in the past decades, at present, only a few non-invasive biomarker tests (such as the immunochemical-based fecal occult blood test and serum/plasma CEA) are available for clinicians in routine CRC management without satisfying accuracy. Recent advancement of omics technologies has greatly accelerated the development of effective biomarkers for various diseases including CRC. Exosomes are cell-derived, lipid-bilayer-enclosed extracellular vesicles (30-100 nm) present in many body fluids and conditioned media of cell cultures. Recent studies have revealed that some tumor exosome membrane proteins can determine organotropic metastasis. Thus, exosome represents an important source of biomarkers. Among the potential exosomal biomarkers including RNAs, proteins and metabolites, we are most interested in the membrane-associated proteins, because they are exposed on the vesicle membrane and possibly detected by appropriate affinity reagents (such as antibodies or aptamers). Using the proteomics platforms and targeted mass spectrometry technology developed in the Proteomics Core of Chang Gung University, we have recently profiled the membrane proteins of exosomes isolated from the conditioned media of 4 CRC cell lines and from the plasma samples pooled respectively from healthy persons and CRC patients, from which numerous membrane proteins showed high potential as novel blood-based CRC biomarkers. In this proposal, we plan to collect more blood samples from healthy persons and CRC patients (with different stages, before and after operation) and then apply the targeted mass spectrometry approach to quantify 57 selected target membrane proteins in the exosomes prepared from plasma of healthy controls (n=100) and CRC patients (n=200). This analysis would allow us to find several exosomal membrane proteins as novel plasma biomarkers or biomarker panels for CRC detection. The effectiveness of these newly identified biomarkers or biomarker panels in disease monitoring of CRC patients will be also evaluated using the longitudinally collected blood samples from the CRC patients after operation.

Project ID:PC10908-0278
External Project ID:MOST109-2320-B182-009-MY3