Novel Liquid Biopsy Biomarkers for Diagnosing and Treating Colorectal Cancer: an Integrated Interrogation of Ctcs, Exosome and Immune Repertoire( I )

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. The recent advancement of omics technologies has revitalized the development of effective biomarkers for various diseases including CRC. Using the multiple omics technology platforms developed in Chang Gung University, our CRC research team has generated plentiful information regarding genomic alterations in many CRC patients by exome sequencing, RNA sequencing, and small RNA sequencing, revealing the differences in gene (mutation) signatures and membrane protein expression pattern between tumor and adjacent non-tumor tissues. In this program project, we plan to extend our preliminary work for identifying novel liquid biopsy biomarkers for early detection and disease monitoring of CRC. We focus on the integrated genomics and proteomics analysis of tumor-associated components, i.e. circulating tumor cells (CTCs) (Subproject 2: Ching-Ping Tseng) and plasma-derived exosomes (Subproject 3: Yung-Ching Hsiao/Jau-Song Yu) and host immune response (T cell repertoires) (Subproject 4: Chiayu Yang/Hsuan Liu) from individual CRC patients before and after treatment (collected from Subproject 1: Jau-Song Yu/Wen-Sy Tsai/Sum-Fu Chiang/Hung-Chih Hsu). The signatures of CTCs, exosome membrane proteins and T-cell receptor repertoires for each patient will be analyzed alone or in combination for identifying novel biomarkers or biomarker panels. We foresee that we can establish novel liquid biopsy biomarkers with strong potential for CRC translational studies. In addition, the results derived from Subprojects 2-4 offer an intriguing possibility for the first time to explore the interactions between tumor-associated components and host immune response in CRC patients by, for example, testing if the membrane proteins specifically associated with tumor-derived components can be recognized by altered T-cell receptors in CRC patients.

Project ID:PC10609-0084
External Project ID:MOST106-2632-B182-002