FGF19 induces the inflammatory phenotype of LX-2 cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE215882 | GEO | 2023/07/03
REPOSITORIES: GEO
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Project description:Purpose. Despite having excellent prognosis when detected early, colorectal cancer (CRC) remains a leading cause of cancer-related deaths globally. Barriers to screening reduces compliance and negatively impacts patient outcomes, necessitating alternatives. A blood-based approach provides a more convenient and accessible modality, but serum markers are lacking. Using a meta-transcriptomics approach, we identified Fibroblast Growth Factor 19 (FGF19), an enteroendocrine FGF responsible for bile acid (BA) homeostasis, as an attractive CRC marker. However, whether FGF19 is aberrantly secreted into blood by colorectal tumors or induces endocrine-like paraneoplastic effects is unknown. Methods. To test if colorectal tumors contribute FGF19 into blood, subcutaneous xenografts of HCT116 and Colo201 cells were established in four male and female NSG mice. Tumor volume, as well as serum and urine FGF19 were assessed over 36 days. Following euthanasia, murine liver was processed for downstream mRNA and bile acid quantification. To determine global paraneoplastic effects of malignant FGF19 on its primary target organ (liver), hepatic mRNA was isolated and subjected to RNA sequencing on an Illumina NovaSeq 6000 system. Reads were processed, aligned, mapped, and analyzed for differential expression and functional enrichment using an integrated informatics pipeline implemented in R. Results. Circulating FGF19 levels derived from subcutaneous xenografts of Colo201, but not HCT116, cells exerted paraneoplastic effects on liver including suppression of BA synthesis, dysregulation of cholesterol metabolism, and induction of pre-neoplasia. Conclusion. Here we report novel paraneoplastic effects of tumor derived FGF19 on liver tissue. Study limitations include in vivo experimentation using two different cell lines, and significant gender-related batch effects in RNA sequencing data.
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