Background: Fecal occult blood test and colonoscopy are the most commonly used modalities for screening colorectal cancer (CRC). However, no matter the stool test or colonoscopy limit the screening uptake because of the inconvenience and discomfort, respectively. The suboptimal screening uptake is a critical challenge for the screening program worldwide. The previous studies demonstrated that blood test is the more acceptable test for CRC screening. However, currently available blood tests fail to detect either CRC or precancerous lesions effectively. It is essential to develop a new blood test to improve the detection of a colorectal neoplasm and, subsequently, increase the uptake of CRC screening.Exosomes are excreted by various cell types, including cancer cells, and play a communicating function between cancer cells. Previous studies have explored that exosome derived from cancer could initiate the generation of pre-metastatic niche at a distal organ. Thus, the exosomal molecules may play a role in detecting colorectal neoplasm as biomarkers. Identification of exosomal molecules specific to colorectal neoplasm in serum provides an opportunity to develop a blood test for detecting neoplasm as a screening test.Aim: To identify the molecules from the tumor-derived exosome in serum as biomarkers for detecting colorectal neoplasm. Hypothesis: The molecules in the tumor-derived exosome are specific to colorectal neoplasm, and can serve as biomarkers for detecting colorectal neoplasm.Material and Methods: The 1st year: Our preliminary data explored that exosomal CD147 in serum significantly higher in CRC than in healthy control. We will investigate the serum level of exosomal CD147 in 223 CRCs, 207 advanced adenomas (AAs), 361 non-AAs, and 524 healthy controls. Exosomal CD147 will be applied as a biomarker to detecting colorectal neoplasm. Moreover, exosomal CD147 will be used in combination with clinical information, other blood tests, and Hb level in stool test to establish a prediction model for stratifying the risk of CRC.The 2nd year: We will identify new exosomal molecules as biomarkers through miRNA array and proteomic experiment. The serum from 25 stage-I CRCs, 25 stage-II CRCs, 25 stage-III CRCs, 25 stage-IV CRCs, 50 AAs, 20 non-AAs, and 30 normal will be used for identifying the molecules specific to each stage of colorectal neoplasm. The high throughput information from the array and proteomics will be used to establish ideal modules via software as biomarkers for detecting colorectal neoplasm. The 3rd year: The prediction model and biomarkers developed in the first two years will be validated in the CRC screening platform. The platform we have established can enroll around 3,000 subjects per year. These people who are enrolled in the platform will have a blood test and fecal immunochemical test (FIT) concurrently. Therefore, we can not only validate the diagnostic performance of the serum biomarkers but also compare its performance with FIT in the platform.Expected results: The exosomal molecules specific to colorectal neoplasm will be identified. The molecules are expected to serve as serum biomarkers for diagnosing colorectal neoplasm. This result will provide an opportunity to develop a blood test for CRC screening and improve the screening uptake.