Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis

Abstract Currently, imaging and serum carcinoembryonic antigen (CEA) tests are not sufficient for early detection and evaluation of metastasis and recurrence in colorectal cancer (CRC). To comprehensively discover and validate more accurate noninvasive biomarkers in urine, we adopted a staged discovery-verification-validation pipeline in 657 urine and 665 tissue samples from healthy controls and CRC patients with a distinct metastatic risk. The diagnostic signature generated combined with serum CEA levels revealed a significantly increased sensitivity (+34.8%) compared to CEA alone. Moreover, over 50% of CEA-negative metastatic patients were correctly predicted by the metastatic signature generated for metastatic risk. The tissue validation and functional study showed that CORO1C was associated with distant metastasis and enhanced the invasion and metastasis of CRC cells via a novel integrin/FAK/SRC and relevant pathways. Our findings provide novel urinary protein biomarkers and potential interventional targets to reliably detect CRC, especially in patients with metastatic CRC.