Colorectal cancer-derived FGF19 is a metabolically active serum biomarker that exerts enteroendocrine effects on...

Despite having excellent prognosis when detected early, colorectal cancer (CRC) remains a leading cause of cancer-related deaths globally. Screening remains an important contributor to CRC survival, but the cost and invasiveness of traditional imaging methodologies can hinder patient compliance. A blood-based approach would be more convenient and accessible, but reliable serum markers are lacking. In this study, the peptide enteroendocrine hormone Fibroblast Growth Factor 19 (FGF19) was identified as an attractive marker for CRC through a meta-transcriptomic analysis. While its pro-tumor effects are documented, FGF19's utility as a blood serum marker for CRC is not well defined. Studies presented here show that FGF19 is constitutively expressed and secreted in 3 of 5 CRC cell lines, and secreted levels increase with seeding density. A subcutaneous CRC cell line-derived xenograft model revealed that FGF19 is detectable in serum of mice injected with FGF19-positive, but not negative, CRC cells at levels corresponding to tumor volume. Enteroendocrine effects of tumor-derived FGF19, including suppression of bile acid synthesis, are evident in liver samples via RNA sequencing and validated by RT-PCR. Notably, the hepatic response to CRC-secreted FGF19 has not been explored prior to this study even though FGF19 is a key regulator of hepatic cholesterol metabolism and bile acid homeostasis. Collectively, these findings support the clinical utility of FGF19 as a putative serum marker for CRC and provide important evidence that CRC-derived FGF19 can modulate liver physiology consistent with the enteroendocrine function of FGF19.